Paresthesia-free spinal cord stimulation occurring at lower frequencies and sweet spot searching using paresthesia

ABSTRACT

Methods and systems for testing and treating spinal cord stimulation (SCS) patients are disclosed. Patients are eventually treated with sub-perception (paresthesia free) therapy. However, supra-perception stimulation is used during “sweet spot searching” during which active electrodes are selected for the patient. This allows sweet spot searching to occur much more quickly and without the need to wash in the various electrode combinations that are tried. After selecting electrodes using supra-perception therapy, therapy is titrated to sub-perception levels using the selected electrodes. Such sub-perception therapy has been investigated using pulses at or below 10 kHz, and it has been determined that a statistically significant correlation exists between pulse width (PW) and frequency (F) in this frequency range at which SCS patients experience significant reduction in symptoms such as back pain. Beneficially, sub-perception stimulation at such low frequencies significantly lowers power consumption in the patient&#39;s neurostimulator.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/100,904, filed Aug. 10, 2018, which is a non-provisional of U.S.Provisional Patent Application Ser. No. 62/544,656, filed Aug. 11, 2017,and 62/693,543, filed Jul. 3, 2018. Priority is claimed to theseapplications, and they are incorporated herein by reference in theirentireties.

FIELD OF THE INVENTION

This application relates to Implantable Medical Devices (IMDs),generally, Spinal Cord Stimulators, more specifically, and to methods ofcontrol of such devices.

INTRODUCTION

Implantable neurostimulator devices are devices that generate anddeliver electrical stimuli to body nerves and tissues for the therapy ofvarious biological disorders, such as pacemakers to treat cardiacarrhythmia, defibrillators to treat cardiac fibrillation, cochlearstimulators to treat deafness, retinal stimulators to treat blindness,muscle stimulators to produce coordinated limb movement, spinal cordstimulators to treat chronic pain, cortical and deep brain stimulatorsto treat motor and psychological disorders, and other neural stimulatorsto treat urinary incontinence, sleep apnea, shoulder subluxation, etc.The description that follows will generally focus on the use of theinvention within a Spinal Cord Stimulation (SCS) system, such as thatdisclosed in U.S. Pat. No. 6,516,227. However, the present invention mayfind applicability with any implantable neurostimulator device system.

An SCS system typically includes an Implantable Pulse Generator (IPG) 10shown in FIG. 1. The IPG 10 includes a biocompatible device case 12 thatholds the circuitry and battery 14 necessary for the IPG to function.The IPG 10 is coupled to electrodes 16 via one or more electrode leads15 that form an electrode array 17. The electrodes 16 are configured tocontact a patient's tissue and are carried on a flexible body 18, whichalso houses the individual lead wires 20 coupled to each electrode 16.The lead wires 20 are also coupled to proximal contacts 22, which areinsertable into lead connectors 24 fixed in a header 23 on the IPG 10,which header can comprise an epoxy for example. Once inserted, theproximal contacts 22 connect to header contacts within the leadconnectors 24, which are in turn coupled by feedthrough pins through acase feedthrough to circuitry within the case 12, although these detailsaren't shown.

In the illustrated IPG 10, there are sixteen lead electrodes (E1-E16)split between two leads 15, with the header 23 containing a 2×1 array oflead connectors 24. However, the number of leads and electrodes in anIPG is application specific and therefore can vary. The conductive case12 can also comprise an electrode (Ec). In a SCS application, theelectrode leads 15 are typically implanted proximate to the dura in apatient's spinal column on the right and left sides of the spinal cordmidline. The proximal electrodes 22 are tunneled through the patient'stissue to a distant location such as the buttocks where the IPG case 12is implanted, at which point they are coupled to the lead connectors 24.In other IPG examples designed for implantation directly at a siterequiring stimulation, the IPG can be lead-less, having electrodes 16instead appearing on the body of the IPG for contacting the patient'stissue. The IPG leads 15 can be integrated with and permanentlyconnected the case 12 in other IPG solutions. The goal of SCS therapy isto provide electrical stimulation from the electrodes 16 to alleviate apatient's symptoms, most notably chronic back pain.

IPG 10 can include an antenna 26 a allowing it to communicatebi-directionally with a number of external devices, as shown in FIG. 4.The antenna 26 a as depicted in FIG. 1 is shown as a conductive coilwithin the case 12, although the coil antenna 26 a can also appear inthe header 23. When antenna 26 a is configured as a coil, communicationwith external devices preferably occurs using near-field magneticinduction. IPG may also include a Radio-Frequency (RF) antenna 26 b. InFIG. 1, RF antenna 26 b is shown within the header 23, but it may alsobe within the case 12. RF antenna 26 b may comprise a patch, slot, orwire, and may operate as a monopole or dipole. RF antenna 26 bpreferably communicates using far-field electromagnetic waves. RFantenna 26 b may operate in accordance with any number of known RFcommunication standards, such as Bluetooth, Zigbee, WiFi, MICS, and thelike.

Stimulation in IPG 10 is typically provided by pulses, as shown in FIG.2. Stimulation parameters typically include the amplitude of the pulses(A; whether current or voltage); the frequency (F) and pulse width (PW)of the pulses; the electrodes 16 (E) activated to provide suchstimulation; and the polarity (P) of such active electrodes, i.e.,whether active electrodes are to act as anodes (that source current tothe tissue) or cathodes (that sink current from the tissue). Thesestimulation parameters taken together comprise a stimulation programthat the IPG 10 can execute to provide therapeutic stimulation to apatient.

In the example of FIG. 2, electrode E5 has been selected as an anode,and thus provides pulses which source a positive current of amplitude+Ato the tissue. Electrode E4 has been selected as a cathode, and thusprovides pulses which sink a corresponding negative current of amplitude−A from the tissue. This is an example of bipolar stimulation, in whichonly two lead-based electrodes are used to provide stimulation to thetissue (one anode, one cathode). However, more than one electrode mayact as an anode at a given time, and more than one electrode may act asa cathode at a given time (e.g., tripole stimulation, quadripolestimulation, etc.).

The pulses as shown in FIG. 2 are biphasic, comprising a first phase 30a, followed quickly thereafter by a second phase 30 b of oppositepolarity. As is known, use of a biphasic pulse is useful in activecharge recovery. For example, each electrodes' current path to thetissue may include a serially-connected DC-blocking capacitor, see,e.g., U.S. Patent Application Publication 2016/0144183, which willcharge during the first phase 30 a and discharged (be recovered) duringthe second phase 30 b. In the example shown, the first and second phases30 a and 30 b have the same duration and amplitude (although oppositepolarities), which ensures the same amount of charge during both phases.However, the second phase 30 b may also be charged balance with thefirst phase 30 a if the integral of the amplitude and durations of thetwo phases are equal in magnitude, as is well known. The width of eachpulse, PW, is defined here as the duration of first pulse phase 30 a,although pulse width could also refer to the total duration of the firstand second pulse phases 30 a and 30 b as well. Note that an interphaseperiod (IP) during which no stimulation is provided may be providedbetween the two phases 30 a and 30 b.

IPG 10 includes stimulation circuitry 28 that can be programmed toproduce the stimulation pulses at the electrodes as defined by thestimulation program. Stimulation circuitry 28 can for example comprisethe circuitry described in U.S. Pat. Nos. 10,576,265, 8,606,362 and8,620,436, and U.S. Patent Application Publication 2018/0071520. Thesereferences are incorporated herein by reference.

FIG. 3 shows an external trial stimulation environment that may precedeimplantation of an IPG 10 in a patient. During external trialstimulation, stimulation can be tried on a prospective implant patientwithout going so far as to implant the IPG 10. Instead, one or moretrial leads 15′ are implanted in the patient's tissue 32 at a targetlocation 34, such as within the spinal column as explained earlier. Theproximal ends of the trial lead(s) 15′ exit an incision 36 and areconnected to an External Trial Stimulator (ETS) 40. The ETS 40 generallymimics operation of the IPG 10, and thus can provide stimulation pulsesto the patient's tissue as explained above. See, e.g., U.S. Pat. No.9,259,574, disclosing a design for an ETS. The ETS 40 is generally wornexternally by the patient for a short while (e.g., two weeks), whichallows the patient and his clinician to experiment with differentstimulation parameters to try and find a stimulation program thatalleviates the patient's symptoms (e.g., pain). If external trialstimulation proves successful, trial lead(s) 15′ are explanted, and afull IPG 10 and lead(s) 15 are implanted as described above; ifunsuccessful, the trial lead(s) 15′ are simply explanted.

Like the IPG 10, the ETS 40 can include one or more antennas to enablebi-directional communications with external devices, explained furtherwith respect to FIG. 4. Such antennas can include a near-fieldmagnetic-induction coil antenna 42 a, and/or a far-field RF antenna 42b, as described earlier. ETS 40 may also include stimulation circuitry44 able to form the stimulation pulses in accordance with a stimulationprogram, which circuitry may be similar to or comprise the samestimulation circuitry 28 present in the IPG 10. ETS 40 may also includea battery (not shown) for operational power.

FIG. 4 shows various external devices that can wirelessly communicatedata with the IPG 10 and the ETS 40, including a patient, hand-heldexternal controller 45, and a clinician programmer 50. Both of devices45 and 50 can be used to send a stimulation program to the IPG 10 or ETS40—that is, to program their stimulation circuitries 28 and 44 toproduce pulses with a desired shape and timing described earlier. Bothdevices 45 and 50 may also be used to adjust one or more stimulationparameters of a stimulation program that the IPG 10 or ETS 40 iscurrently executing. Devices 45 and 50 may also receive information fromthe IPG 10 or ETS 40, such as various status information, etc.

External controller 45 can be as described in U.S. Patent ApplicationPublication 2015/0080982 for example, and may comprise either adedicated controller configured to work with the IPG 10. Externalcontroller 45 may also comprise a general purpose mobile electronicsdevice such as a mobile phone which has been programmed with a MedicalDevice Application (MDA) allowing it to work as a wireless controllerfor the IPG 10 or ETS 40, as described in U.S. Patent ApplicationPublication 2015/0231402. External controller 45 includes a userinterface, including means for entering commands (e.g., buttons oricons) and a display 46. The external controller 45's user interfaceenables a patient to adjust stimulation parameters, although it may havelimited functionality when compared to the more-powerful clinicianprogrammer 50, described shortly.

The external controller 45 can have one or more antennas capable ofcommunicating with the IPG 10 and ETS 40. For example, the externalcontroller 45 can have a near-field magnetic-induction coil antenna 47 acapable of wirelessly communicating with the coil antenna 26 a or 42 ain the IPG 10 or ETS 40. The external controller 45 can also have afar-field RF antenna 47 b capable of wirelessly communicating with theRF antenna 26 b or 42 b in the IPG 10 or ETS 40.

The external controller 45 can also have control circuitry 48 such as amicroprocessor, microcomputer, an FPGA, other digital logic structures,etc., which is capable of executing instructions an electronic device.Control circuitry 48 can for example receive patient adjustments tostimulation parameters, and create a stimulation program to bewirelessly transmitted to the IPG 10 or ETS 40.

Clinician programmer 50 is described further in U.S. Patent ApplicationPublication 2015/0360038, and is only briefly explained here. Theclinician programmer 50 can comprise a computing device 51, such as adesktop, laptop, or notebook computer, a tablet, a mobile smart phone, aPersonal Data Assistant (PDA)-type mobile computing device, etc. In FIG.4, computing device 51 is shown as a laptop computer that includestypical computer user interface means such as a screen 52, a mouse, akeyboard, speakers, a stylus, a printer, etc., not all of which areshown for convenience. Also shown in FIG. 4 are accessory devices forthe clinician programmer 50 that are usually specific to its operationas a stimulation controller, such as a communication “wand” 54, and ajoystick 58, which are coupleable to suitable ports on the computingdevice 51, such as USB ports 59 for example.

The antenna used in the clinician programmer 50 to communicate with theIPG 10 or ETS 40 can depend on the type of antennas included in thosedevices. If the patient's IPG 10 or ETS 40 includes a coil antenna 26 aor 42 a, wand 54 can likewise include a coil antenna 56 a to establishnear-filed magnetic-induction communications at small distances. In thisinstance, the wand 54 may be affixed in close proximity to the patient,such as by placing the wand 54 in a belt or holster wearable by thepatient and proximate to the patient's IPG 10 or ETS 40.

If the IPG 10 or ETS 40 includes an RF antenna 26 b or 42 b, the wand54, the computing device 51, or both, can likewise include an RF antenna56 b to establish communication with the IPG 10 or ETS 40 at largerdistances. (Wand 54 may not be necessary in this circumstance). Theclinician programmer 50 can also establish communication with otherdevices and networks, such as the Internet, either wirelessly or via awired link provided at an Ethernet or network port.

To program stimulation programs or parameters for the IPG 10 or ETS 40,the clinician interfaces with a clinician programmer graphical userinterface (GUI) 64 provided on the display 52 of the computing device51. As one skilled in the art understands, the GUI 64 can be rendered byexecution of clinician programmer software 66 on the computing device51, which software may be stored in the device's non-volatile memory 68.One skilled in the art will additionally recognize that execution of theclinician programmer software 66 in the computing device 51 can befacilitated by control circuitry 70 such as a microprocessor,microcomputer, an FPGA, other digital logic structures, etc., which iscapable of executing programs in a computing device. Such controlcircuitry 70, in addition to executing the clinician programmer software66 and rendering the GUI 64, can also enable communications via antennas56 a or 56 b to communicate stimulation parameters chosen through theGUI 64 to the patient's IPG 10.

A portion of the GUI 64 is shown in one example in FIG. 5. One skilledin the art will understand that the particulars of the GUI 64 willdepend on where clinician programmer software 66 is in its execution,which will depend on the GUI selections the clinician has made. FIG. 5shows the GUI 64 at a point allowing for the setting of stimulationparameters for the patient and for their storage as a stimulationprogram. To the left a program interface 72 is shown, which as explainedfurther in the '038 Publication allows for naming, loading and saving ofstimulation programs for the patient. Shown to the right is astimulation parameters interface 82, in which specific stimulationparameters (A, D, F, E, P) can be defined for a stimulation program.Values for stimulation parameters relating to the shape of the waveform(A; in this example, current), pulse width (PW), and frequency (F) areshown in a waveform parameter interface 84, including buttons theclinician can use to increase or decrease these values.

Stimulation parameters relating to the electrodes 16 (the electrodes Eactivated and their polarities P), are made adjustable in an electrodeparameter interface 86. Electrode stimulation parameters are alsovisible and can be manipulated in a leads interface 92 that displays theleads 15 (or 15′) in generally their proper position with respect toeach other, for example, on the left and right sides of the spinalcolumn. A cursor 94 (or other selection means such as a mouse pointer)can be used to select a particular electrode in the leads interface 92.Buttons in the electrode parameter interface 86 allow the selectedelectrode (including the case electrode, Ec) to be designated as ananode, a cathode, or off. The electrode parameter interface 86 furtherallows the relative strength of anodic or cathodic current of theselected electrode to be specified in terms of a percentage, X. This isparticularly useful if more than one electrode is to act as an anode orcathode at a given time, as explained in the '038 Publication. Inaccordance with the example waveforms shown in FIG. 2, as shown in theleads interface 92, electrode E5 has been selected as the only anode tosource current, and this electrode receives X=100% of the specifiedanodic current, +A. Likewise, electrode E4 has been selected as the onlycathode to sink current, and this electrode receives X=100% of thatcathodic current, −A.

The GUI 64 as shown specifies only a pulse width PW of the first pulsephase 30 a. The clinician programmer software 66 that runs and receivesinput from the GUI 64 will nonetheless ensure that the IPG 10 and ETS 40are programmed to render the stimulation program as biphasic pulses ifbiphasic pulses are to be used. For example, the clinician programmingsoftware 66 can automatically determine durations and amplitudes forboth of the pulse phases 30 a and 30 b (e.g., each having a duration ofPW, and with opposite polarities+A and −A). An advanced menu 88 can alsobe used (among other things) to define the relative durations andamplitudes of the pulse phases 30 a and 30 b, and to allow for othermore advance modifications, such as setting of a duty cycle (on/offtime) for the stimulation pulses, and a ramp-up time over whichstimulation reaches its programmed amplitude (A), etc. A mode menu 90allows the clinician to choose different modes for determiningstimulation parameters. For example, as described in the '038Publication, mode menu 90 can be used to enable electronic trolling,which comprises an automated programming mode that performs currentsteering along the electrode array by moving the cathode in a bipolarfashion.

While GUI 64 is shown as operating in the clinician programmer 50, theuser interface of the external controller 45 may provide similarfunctionality.

SUMMARY

In a first example, a method is disclosed for programming a spinal cordstimulator having a plurality of electrodes comprising an array, whichmay comprise: programming the spinal cord stimulator implanted in apatient to generate stimulation pulses of a shape comprising a frequencyand a pulse width to at least two of a plurality of electrodes, whereinthe frequency and the pulse width are selected based on informationrelating frequencies and pulse widths at which stimulation pulses areformed to provide pain relief to the patient without paresthesia.

The stimulation pulses may form a bipole in the patient's tissue. Thespinal cord stimulator may be programmed to generate stimulation pulsesto at least three of the plurality of electrodes to form a virtualbipole in the patient's tissue.

The spinal cord stimulator may further comprise control circuitry,wherein the information is stored in the control circuitry. Thefrequency may be provided to the control circuitry, and the pulse widthmay be determined using the information. The pulse width may be providedto the control circuitry, and the frequency may be determined using theinformation. The information may be stored in control circuitry of anexternal device used to program the spinal cord stimulator. The controlcircuitry may determine using the information at least one of thefrequency or the pulse width at which stimulation pulses are formed toprovide pain relief without paresthesia, and the control circuitry mayfurther wirelessly transmit the at least one of the frequency or thepulse width to the spinal cord stimulator. The frequency and pulse widthmay be selected using the information as a frequency and pulse widththat requires a lowest amount of power for the stimulation pulses.

Each of the stimulation pulses may comprise a biphasic pulse having afirst phase of a first polarity and a second phase of a second polarityopposite the first polarity, wherein the first and second phases areactively driven by stimulation circuitry in the spinal cord stimulator.Each of the stimulation pulses may comprise a symmetric biphasic pulse,wherein a duration of the first phase is equal to a duration of thesecond phase, and wherein an amplitude of the first phase is equal butof opposite polarity to an amplitude of the second phase. The pulsewidth may comprise (i) a total duration of the first and second phases,or (ii) a duration of either the first phase or the second phase.

The frequency may be 1 kHz, or lower than 1 kHz. The frequency and pulsewidth at which stimulation pulses are formed to provide pain reliefwithout paresthesia may be on or within a linearly-bounded regiondefined by points

-   -   (10 Hz, 265 μs), (10 Hz, 435 μs), (50 Hz, 370 μs), and (50 Hz,        230 μs),    -   (50 Hz, 230 μs), (50 Hz, 370 μs), (100 Hz, 325 μs), and (100 Hz,        195 μs),    -   (100 Hz, 195 μs), (100 Hz, 325 μs), (200 Hz, 260 μs), and (200        Hz, 160 μs),    -   (200 Hz, 160 μs), (200 Hz, 260 μs), (400 Hz, 225 μs), and (400        Hz, 140 μs),    -   (400 Hz, 140 μs), (400 Hz, 225 μs), (600 Hz, 200 μs), and (600        Hz, 120 μs),    -   (600 Hz, 120 μs), (600 Hz, 200 μs), (800 Hz, 175 μs), and (800        Hz, 105 μs), or    -   (800 Hz, 105 μs), (800 Hz, 175 μs), (1000 Hz, 150 μs), and (1000        Hz, 90 μs).

The frequency and pulse width at which stimulation pulses are formed toprovide pain relief without paresthesia may not comprise a duty cyclerelating frequency and pulse width that is constant lower than 1 kHz.

The frequency may be in a range of 1 kHz to 10 kHz. The frequency andpulse width at which stimulation pulses are formed to provide painrelief without paresthesia may be on or within one or morelinearly-bounded regions defined by points:

-   -   (i) (1 kHz, 98.3 μs), (1 kHz, 109 μs), (4 kHz, 71.4 μs), and (4        kHz, 64.6 μs); or    -   (ii) (4 kHz, 71.4 μs), (4 kHz, 64.6 μs), (7 kHz, 44.2 μs), and        (7 kHz, 48.8 μs); or    -   (iii) (7 kHz, 44.2 μs), (7 kHz, 48.8 μs), (10 kHz, 29.9 μs), and        (10 kHz, 27.1 μs).    -   or    -   (i) (1 kHz, 96.3 μs), (1 kHz, 112 μs), (4 kHz, 73.8 μs), and (4        kHz, 62.2 μs); or    -   (ii) (4 kHz, 73.8 μs), (4 kHz, 62.2 μs), (7 kHz, 43.6 μs), and        (7 kHz, 49.4 μs); or    -   (iii) (7 kHz, 43.6 μs), (7 kHz, 49.4 μs), (10 kHz, 30.0 μs), and        (10 kHz, 27.0 μs).    -   or    -   (i) (1 kHz, 69.6 μs), (1 kHz, 138.4 μs), (4 kHz, 93.9 μs), and        (4 kHz, 42.1 μs); or    -   (ii) (4 kHz, 93.9 μs), (4 kHz, 42.1 μs), (7 kHz, 33.4 μs), and        (7 kHz, 59.6 μs); or    -   (iii) (7 kHz, 33.4 μs), (7 kHz, 59.6 μs), (10 kHz, 35.2 μs), and        (10 kHz, 21.8 μs).    -   or    -   (i) (1 kHz, 50.0 μs), (1 kHz, 200.0 μs), (4 kHz, 110.0 μs), and        (4 kHz, 30.0 μs); or    -   (ii) (4 kHz, 110.0 μs), (4 kHz, 30.0 μs), (7 kHz, 30.0 μs), and        (7 kHz, 60.0 μs); or    -   (iii) (7 kHz, 30.0 μs), (7 kHz, 60.0 μs), (10 kHz, 40.0 μs), and        (10 kHz, 20.0 μs).

The method may further comprise steering current between the pluralityof electrodes to adjust a location at which the stimulation pulses areapplied to the patient. The method may further comprise adjusting anamplitude of the stimulation pulses based on the adjusted location atwhich the stimulation pulses are applied to the patient.

The frequency, pulse width, and amplitude may comprise three of a set ofstimulation parameters used to generate the stimulation pulses, and themethod may further comprise reducing at least one of the stimulationparameters to or by a set amount or percentage in response to aninstruction. The stimulation circuitry in response to the instructionmay reduce the amplitude of the stimulation pulses to or by a set amountor percentage.

The frequency and pulse width may comprise two of a set of stimulationparameters used to generate the stimulation pulses, and the method mayfurther comprise adjusting at least one of the stimulation parameters inresponse to a change in position or activity of the patient. The spinalcord stimulator may be programmed during a programming session, and thestimulation pulses may be washed in for a period of one hour or lessduring the programming session to provide pain relief to the patientwithout paresthesia.

In a second example, a system is disclosed, which may comprise: a spinalcord stimulator, comprising stimulation circuitry programmed to generatestimulation pulses of a shape comprising a frequency and a pulse widthto at least one of a plurality of electrodes, wherein the frequency andthe pulse width are selected based on information relating frequenciesand pulse widths at which stimulation pulses are formed to provide painrelief without paresthesia.

The stimulation pulses may be configured to form a bipole in thepatient's tissue. The stimulation circuitry may be programmed togenerate stimulation pulses to at least three of the plurality ofelectrodes to form a virtual bipole in the patient's tissue. The spinalcord stimulator may further comprise control circuitry, wherein theinformation is stored in the control circuitry. The frequency may beprovided to the control circuitry, and the pulse width may be determinedusing the information. The pulse width may be provided to the controlcircuitry, and the frequency may be determined using the information.

The system may further comprise an external device comprising controlcircuitry, wherein the information is stored in the control circuitry.The control circuitry may be configured to determine using theinformation at least one of the frequency or the pulse width at whichstimulation pulses are formed to provide pain relief withoutparesthesia, and wherein the control circuitry is further configured towirelessly transmit the at least one of the frequency or the pulse widthto the spinal cord stimulator.

The frequency and pulse width may be selected using the information as afrequency and pulse width that requires a lowest amount of power for thestimulation pulses.

Each of the stimulation pulses may comprise a biphasic pulse having afirst phase of a first polarity and a second phase of a second polarityopposite the first polarity, wherein the first and second phases areactively driven by stimulation circuitry in the spinal cord stimulator.Each of the stimulation pulses may comprise a symmetric biphasic pulse,wherein a duration of the first phase is equal to a duration of thesecond phase, and wherein an amplitude of the first phase is equal butof opposite polarity to an amplitude of the second phase. The pulsewidth may comprise (i) a total duration of the first and second phases,or (ii) a duration of either the first phase or the second phase.

The frequency may be 1 kHz or lower than 1 kHz. The frequency and pulsewidth at which stimulation pulses are formed to provide pain reliefwithout paresthesia are on or within a linearly-bounded region definedby points

-   -   (10 Hz, 265 μs), (10 Hz, 435 μs), (50 Hz, 370 μs), and (50 Hz,        230 μs),    -   (50 Hz, 230 μs), (50 Hz, 370 μs), (100 Hz, 325 μs), and (100 Hz,        195 μs),    -   (100 Hz, 195 μs), (100 Hz, 325 μs), (200 Hz, 260 μs), and (200        Hz, 160 μs),    -   (200 Hz, 160 μs), (200 Hz, 260 μs), (400 Hz, 225 μs), and (400        Hz, 140 μs),    -   (400 Hz, 140 μs), (400 Hz, 225 μs), (600 Hz, 200 μs), and (600        Hz, 120 μs),    -   (600 Hz, 120 μs), (600 Hz, 200 μs), (800 Hz, 175 μs), and (800        Hz, 105 μs), or    -   (800 Hz, 105 μs), (800 Hz, 175 μs), (1000 Hz, 150 μs), and (1000        Hz, 90 μs).

The frequency and pulse width at which stimulation pulses are formed toprovide pain relief without paresthesia may not comprise a duty cyclerelating frequency and pulse width that is constant in a range of 10 Hzthrough 1 kHz.

The frequency may be in a range of 1 kHz to 10 kHz. The frequency andpulse width at which stimulation pulses are formed to provide painrelief without paresthesia may be on or within one or morelinearly-bounded regions defined by points:

-   -   (i) (1 kHz, 98.3 μs), (1 kHz, 109 μs), (4 kHz, 71.4 μs), and (4        kHz, 64.6 μs); or    -   (ii) (4 kHz, 71.4 μs), (4 kHz, 64.6 μs), (7 kHz, 44.2 μs), and        (7 kHz, 48.8 μs); or    -   (iii) (7 kHz, 44.2 μs), (7 kHz, 48.8 μs), (10 kHz, 29.9 μs), and        (10 kHz, 27.1 μs).    -   or    -   (i) (1 kHz, 96.3 μs), (1 kHz, 112 μs), (4 kHz, 73.8 μs), and (4        kHz, 62.2 μs); or    -   (ii) (4 kHz, 73.8 μs), (4 kHz, 62.2 μs), (7 kHz, 43.6 μs), and        (7 kHz, 49.4 μs); or    -   (iii) (7 kHz, 43.6 μs), (7 kHz, 49.4 μs), (10 kHz, 30.0 μs), and        (10 kHz, 27.0 μs).    -   or    -   (i) (1 kHz, 69.6 μs), (1 kHz, 138.4 μs), (4 kHz, 93.9 μs), and        (4 kHz, 42.1 μs); or    -   (ii) (4 kHz, 93.9 μs), (4 kHz, 42.1 μs), (7 kHz, 33.4 μs), and        (7 kHz, 59.6 μs); or    -   (iii) (7 kHz, 33.4 μs), (7 kHz, 59.6 μs), (10 kHz, 35.2 μs), and        (10 kHz, 21.8 μs).    -   or    -   (i) (1 kHz, 50.0 μs), (1 kHz, 200.0 μs), (4 kHz, 110.0 μs), and        (4 kHz, 30.0 μs); or    -   (ii) (4 kHz, 110.0 μs), (4 kHz, 30.0 μs), (7 kHz, 30.0 μs), and        (7 kHz, 60.0 μs); or    -   (iii) (7 kHz, 30.0 μs), (7 kHz, 60.0 μs), (10 kHz, 40.0 μs), and        (10 kHz, 20.0 μs).

The stimulation circuitry may be configurable to steer current betweenthe plurality of electrodes to adjust a location at which thestimulation pulses are applied to the patient. The stimulation circuitrymay be further configured to adjust an amplitude of the stimulationpulses based on the adjusted location at which the stimulation pulsesare applied to the patient.

The frequency, pulse width, and amplitude may comprise three of a set ofstimulation parameters used to generate the stimulation pulses, whereinthe stimulation circuitry is configurable in response to an instructionto reduce at least one of the stimulation parameters to or by a setamount or percentage.

The frequency and pulse width may comprise two of a set of stimulationparameters used to generate the stimulation pulses, and wherein thestimulation circuitry is configurable to adjust at least one of thestimulation parameters in response to a change in position or activityof the patient.

The spinal cord stimulator may be configured to be programmable during aprogramming session, and wherein the spinal cord stimulator isconfigured to wash in the stimulation pulses for a period of one hour orless during the programming session to provide pain relief to thepatient without paresthesia.

In a third example, a method is disclosed for programming a spinal cordstimulator having a plurality of electrodes comprising an array, whichmay comprise: (a) providing to the spinal cord stimulator a plurality ofdifferent sets of first stimulation parameters, wherein each firststimulation parameters set causes the spinal cord stimulator to formbiphasic test pulses at at least two of the electrodes, wherein eachbiphasic test pulse comprises a first phase of a first polarity and asecond phase of a second polarity opposite the first polarity, whereinthe first and second pulse phases are both actively driven bystimulation circuitry in the spinal cord stimulator, and wherein eachfirst stimulation parameters set causes supra-perception stimulation tooccur at different locations relative to the array; (b) determining aset of the first stimulation parameters that treats a pain symptom ofthe patient, the determined first stimulation parameters setcorresponding to a therapy location relative to the array; and (c)providing to the spinal cord stimulator a set of second stimulationparameters to cause the spinal cord stimulator to form therapeuticpulses at at least two of the electrodes, wherein the second stimulationparameters set causes sub-perception stimulation to occur at the therapylocation.

The biphasic test pulses may be formed at 130 Hz or less. A charge ofthe first phase may equal a charge of the second phase. A duration ofthe first phase may be different from a duration of the second phase,and an amplitude of the first phase may be different from an amplitudeof the second phase. The biphasic test pulses may comprise symmetricbiphasic pulses, wherein a duration of the first phase is equal to aduration of the second phase, and wherein an amplitude of the firstphase is equal to but of opposite polarity to an amplitude of the secondphase. A charge of the first phase may not equal a charge of the secondphase.

The therapeutic pulses may comprise biphasic pulses having a first phaseof a first polarity and a second phase of a second polarity opposite thefirst polarity. The therapeutic pulses may comprise symmetric biphasicpulses, wherein a duration of the first phase is equal to a duration ofthe second phase, and wherein an amplitude of the first phase is equalbut of opposite polarity to an amplitude of the second phase.

The second stimulation parameters set may determined by adjusting atleast one of the stimulation parameters of the determined firststimulation parameters set without adjusting the therapy locationrelative to the array. The determined first stimulation parameters setmay comprise a set of stimulation parameters to which the patientresponds favorably to treatment of the pain symptom.

Each first stimulation parameters set may cause supra-perceptionstimulation to occur as a multipole at the different locations. At leastsome or all of the first stimulation parameters sets may causesupra-perception to occur as a bipole at the different locations. Atleast some of the first stimulation parameters sets may causesupra-perception stimulation to occur as a virtual bipole at thedifferent locations. The second stimulation parameters may causesub-perception stimulation to occur as a multipole at the therapylocation. The second stimulation parameters may cause sub-perceptionstimulation to occur as a bipole at the therapy location. The secondstimulation parameters may cause sub-perception stimulation to occur asa virtual bipole at the therapy location.

The determined first stimulation parameters set may be determined usingfeedback from the patient. The determined first stimulation parametersset may comprise an amplitude of the test pulses, and wherein the set ofsecond stimulation parameters comprises an amplitude of the therapeuticpulses, and wherein the amplitude of the therapeutic pulses is lowerthan the amplitude of the test pulses. The determined first stimulationparameters set may differ from the second stimulation parameters setonly in the amplitudes of the test and therapeutic pulses.

Each first stimulation parameters set and the second stimulationparameters set may comprise an indication of which of the at least twoelectrodes are active, an indication of the polarity of the at least twoelectrodes, and an indication of an amplitude of a current at the atleast two electrodes.

The second stimulation parameters set may comprise a frequency and pulsewidth of the therapeutic pulses, wherein the frequency is 10 kHz orlower, and wherein at least one of the frequency and the pulse width areselected to cause the sub-perception stimulation to occur. The selectedfrequency and pulse width may be on or within one or morelinearly-bounded regions defined by points:

-   -   (i) (10 Hz, 265 μs), (10 Hz, 435 μs), (50 Hz, 370 μs), and (50        Hz, 230 μs); or    -   (ii) (50 Hz, 230 μs), (50 Hz, 370 μs), (100 Hz, 325 μs), and        (100 Hz, 195 μs); or    -   (iii) (100 Hz, 195 μs), (100 Hz, 325 μs), (200 Hz, 260 μs), and        (200 Hz, 160 μs); or    -   (iv) (200 Hz, 160 μs), (200 Hz, 260 μs), (400 Hz, 225 μs), and        (400 Hz, 140 μs); or    -   (v) (400 Hz, 140 μs), (400 Hz, 225 μs), (600 Hz, 200 μs), and        (600 Hz, 120 μs); or    -   (vi) (600 Hz, 120 μs), (600 Hz, 200 μs), (800 Hz, 175 μs), and        (800 Hz, 105 μs); or    -   (vii) (800 Hz, 105 μs), (800 Hz, 175 μs), (1000 Hz, 150 μs), and        (1000 Hz, 90 μs).

The selected frequency and pulse width may be on or within one or morelinearly-bounded regions defined by points:

(i) (1 kHz, 98.3 μs), (1 kHz, 109 μs), (4 kHz, 71.4 μs), and (4 kHz,64.6 μs); or

-   -   (ii) (4 kHz, 71.4 μs), (4 kHz, 64.6 μs), (7 kHz, 44.2 μs), and        (7 kHz, 48.8 μs); or    -   (iii) (7 kHz, 44.2 μs), (7 kHz, 48.8 μs), (10 kHz, 29.9 μs), and        (10 kHz, 27.1 μs). or    -   (i) (1 kHz, 96.3 μs), (1 kHz, 112 μs), (4 kHz, 73.8 μs), and (4        kHz, 62.2 μs); or    -   (ii) (4 kHz, 73.8 μs), (4 kHz, 62.2 μs), (7 kHz, 43.6 μs), and        (7 kHz, 49.4 μs); or    -   (iii) (7 kHz, 43.6 μs), (7 kHz, 49.4 μs), (10 kHz, 30.0 μs), and        (10 kHz, 27.0 μs). or    -   (i) (1 kHz, 69.6 μs), (1 kHz, 138.4 μs), (4 kHz, 93.9 μs), and        (4 kHz, 42.1 μs); or    -   (ii) (4 kHz, 93.9 μs), (4 kHz, 42.1 μs), (7 kHz, 33.4 μs), and        (7 kHz, 59.6 μs); or    -   (iii) (7 kHz, 33.4 μs), (7 kHz, 59.6 μs), (10 kHz, 35.2 μs), and        (10 kHz, 21.8 μs). or    -   (i) (1 kHz, 50.0 μs), (1 kHz, 200.0 μs), (4 kHz, 110.0 μs), and        (4 kHz, 30.0 μs); or    -   (ii) (4 kHz, 110.0 μs), (4 kHz, 30.0 μs), (7 kHz, 30.0 μs), and        (7 kHz, 60.0 μs); or    -   (iii) (7 kHz, 30.0 μs), (7 kHz, 60.0 μs), (10 kHz, 40.0 μs), and        (10 kHz, 20.0 μs).

The frequency and the pulse width may be selected based on informationrelating frequencies and pulse widths at which the therapeutic pulsesare formed to cause sub-perception stimulation to occur at the therapylocation. The first and second stimulation parameters set may beprovided to the spinal cord stimulator by an external device, andwherein the information is stored on the external device. Theinformation may be stored in the spinal cord stimulator. The frequencyand pulse width may be selected using the information as a frequency andpulse width that requires a lowest amount of power for the therapeuticpulses.

The method may further comprise steering current between the pluralityof electrodes to adjust the therapy location to a new therapy locationrelative to the array. The method may further comprise adjusting anamplitude of the therapeutic pulses based on the new therapy location.

The determined first stimulation parameters set may comprises an firstamplitude of the test pulses, and the method may further comprise, inresponse to an instruction, deriving the second stimulation parametersset from the determined first stimulation parameter set by reducing thefirst amplitude to a second amplitude for the therapeutic pulses. Thefirst amplitude may be reduced to the second amplitude to or by a setamount or percentage.

The method may further comprise adjusting at least one of thestimulation parameters of the second stimulation parameters set inresponse to a change in position or activity of the patient. The spinalcord stimulator may programmed during a programming session, and thetherapeutic pulses may be washed in for a period of one hour or lessduring the programming session to causes sub-perception stimulation tooccur at the therapy location.

In a fourth example, a system is for programming a spinal cordstimulator having a plurality of electrodes comprising an array, whichmay comprise: an external system a non-transitory computer readablemedia containing instructions that when executed allows the externaldevice to provide to the spinal cord stimulator a plurality of differentsets of first stimulation parameters, wherein each first stimulationparameters set causes the spinal cord stimulator to form biphasic testpulses at at least two of the electrodes, wherein each biphasic testpulse comprises a first phase of a first polarity and a second phase ofa second polarity opposite the first polarity, wherein the first andsecond pulse phases are both actively driven by stimulation circuitry inthe spinal cord stimulator, and wherein each first stimulationparameters set causes supra-perception stimulation to occur at differentlocations relative to the array; wherein after determining a set of thefirst stimulation parameters that treats a pain symptom of the patient,the determined first stimulation parameters set corresponding to atherapy location relative to the array, the instructions when executedfurther allow the external device to provide to the spinal cordstimulator a set of second stimulation parameters to cause the spinalcord stimulator to form therapeutic pulses at at least two of theelectrodes, wherein the second stimulation parameters set causessub-perception stimulation to occur at the therapy location.

The biphasic test pulses may be formed at 130 Hz or less. A charge ofthe first phase may equal a charge of the second phase. A duration ofthe first phase may be different from a duration of the second phase,and an amplitude of the first phase may be different from an amplitudeof the second phase. The biphasic test pulses may comprise symmetricbiphasic pulses, wherein a duration of the first phase is equal to aduration of the second phase, and wherein an amplitude of the firstphase is equal to but of opposite polarity to an amplitude of the secondphase. A charge of the first phase may not equal a charge of the secondphase.

The therapeutic pulses may comprise biphasic pulses having a first phaseof a first polarity and a second phase of a second polarity opposite thefirst polarity. The therapeutic pulses may comprise symmetric biphasicpulses, wherein a duration of the first phase is equal to a duration ofthe second phase, and wherein an amplitude of the first phase is equalbut of opposite polarity to an amplitude of the second phase.

The non-transitory computer readable media may be configured todetermine the second stimulation parameters set by adjusting at leastone of the stimulation parameters of the determined first stimulationparameters set without adjusting the therapy location relative to thearray. The determined first stimulation parameters set may comprise aset of stimulation parameters to which the patient responds favorably totreatment of the pain symptom.

Each first stimulation parameters set may cause supra-perceptionstimulation to occur as a multipole at the different locations. At leastsome or all of the first stimulation parameters sets may causesupra-perception to occur as a bipole at the different locations. Atleast some of the first stimulation parameters sets may causesupra-perception stimulation to occur as a virtual bipole at thedifferent locations. The second stimulation parameters may causesub-perception stimulation to occur as a multipole at the therapylocation. The second stimulation parameters may cause sub-perceptionstimulation to occur as a bipole at the therapy location. The secondstimulation parameters may cause sub-perception stimulation to occur asa virtual bipole at the therapy location.

The determined first stimulation parameters set may be determined usingfeedback from the patient. The determined first stimulation parametersset may comprise an amplitude of the test pulses, and wherein the set ofsecond stimulation parameters comprises an amplitude of the therapeuticpulses, and wherein the amplitude of the therapeutic pulses is lowerthan the amplitude of the test pulses. The determined first stimulationparameters set may differ from the second stimulation parameters setonly in the amplitudes of the test and therapeutic pulses.

Each first stimulation parameters set and the second stimulationparameters set may comprise an indication of which of the at least twoelectrodes are active, an indication of the polarity of the at least twoelectrodes, and an indication of an amplitude of a current at the atleast two electrodes.

The second stimulation parameters set may comprise a frequency and pulsewidth of the therapeutic pulses, wherein the frequency is 10 kHz orlower, and wherein at least one of the frequency and the pulse width areselected by the computer readable media to cause the sub-perceptionstimulation to occur. The selected frequency and pulse width may be onor within one or more linearly-bounded regions defined by points:

-   -   (i) (10 Hz, 265 μs), (10 Hz, 435 μs), (50 Hz, 370 μs), and (50        Hz, 230 μs); or    -   (ii) (50 Hz, 230 μs), (50 Hz, 370 μs), (100 Hz, 325 μs), and        (100 Hz, 195 μs); or    -   (iii) (100 Hz, 195 μs), (100 Hz, 325 μs), (200 Hz, 260 μs), and        (200 Hz, 160 μs); or    -   (iv) (200 Hz, 160 μs), (200 Hz, 260 μs), (400 Hz, 225 μs), and        (400 Hz, 140 μs); or    -   (v) (400 Hz, 140 μs), (400 Hz, 225 μs), (600 Hz, 200 μs), and        (600 Hz, 120 μs); or    -   (vi) (600 Hz, 120 μs), (600 Hz, 200 μs), (800 Hz, 175 μs), and        (800 Hz, 105 μs); or    -   (vii) (800 Hz, 105 μs), (800 Hz, 175 μs), (1000 Hz, 150 μs), and        (1000 Hz, 90 μs).

The selected frequency and pulse width may be on or within one or morelinearly-bounded regions defined by points:

-   -   (i) (1 kHz, 98.3 μs), (1 kHz, 109 μs), (4 kHz, 71.4 μs), and (4        kHz, 64.6 μs); or    -   (ii) (4 kHz, 71.4 μs), (4 kHz, 64.6 μs), (7 kHz, 44.2 μs), and        (7 kHz, 48.8 μs); or    -   (iii) (7 kHz, 44.2 μs), (7 kHz, 48.8 μs), (10 kHz, 29.9 μs), and        (10 kHz, 27.1 μs). or    -   (i) (1 kHz, 96.3 μs), (1 kHz, 112 μs), (4 kHz, 73.8 μs), and (4        kHz, 62.2 μs); or    -   (ii) (4 kHz, 73.8 μs), (4 kHz, 62.2 μs), (7 kHz, 43.6 μs), and        (7 kHz, 49.4 μs); or    -   (iii) (7 kHz, 43.6 μs), (7 kHz, 49.4 μs), (10 kHz, 30.0 μs), and        (10 kHz, 27.0 μs). or    -   (i) (1 kHz, 69.6 μs), (1 kHz, 138.4 μs), (4 kHz, 93.9 μs), and        (4 kHz, 42.1 μs); or    -   (ii) (4 kHz, 93.9 μs), (4 kHz, 42.1 μs), (7 kHz, 33.4 μs), and        (7 kHz, 59.6 μs); or    -   (iii) (7 kHz, 33.4 μs), (7 kHz, 59.6 μs), (10 kHz, 35.2 μs), and        (10 kHz, 21.8 μs). or    -   (i) (1 kHz, 50.0 μs), (1 kHz, 200.0 μs), (4 kHz, 110.0 μs), and        (4 kHz, 30.0 μs); or    -   (ii) (4 kHz, 110.0 μs), (4 kHz, 30.0 μs), (7 kHz, 30.0 μs), and        (7 kHz, 60.0 μs); or    -   (iii) (7 kHz, 30.0 μs), (7 kHz, 60.0 μs), (10 kHz, 40.0 μs), and        (10 kHz, 20.0 μs).

The frequency and the pulse width may be selected by the computerreadable media based on information relating frequencies and pulsewidths at which the therapeutic pulses are formed to causesub-perception stimulation to occur at the therapy location. Thefrequency and pulse width may be selected using the information as afrequency and pulse width that requires a lowest amount of power for thetherapeutic pulses.

The computer readable media may contains instructions that when executedallow the external device to steer current between the plurality ofelectrodes to adjust the therapy location to a new therapy locationrelative to the array. The computer readable media may further containsinstructions that when executed allow the external device to adjust anamplitude of the therapeutic pulses based on the new therapy location.The computer readable media may further contain instructions that whenexecuted allow the external device to reduce at least one of thestimulation parameters of the second stimulation parameters set to or bya set amount or percentage.

The computer readable media may further contain instructions that whenexecuted allow the external device to adjust at least one of thestimulation parameters of the second stimulation parameters set inresponse to a change in position or activity of the patient. Thecomputer readable media may further contain instructions that whenexecuted allow the external device to program the spinal cord stimulatorduring a programming session, and wherein the instructions areconfigured to wash in the therapeutic pulses for a period of one hour orless during the programming session to causes sub-perception stimulationto occur at the therapy location.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an Implantable Pulse Generator (IPG) useable for SpinalCord Stimulation (SC S), in accordance with the prior art.

FIG. 2 shows an example of stimulation pulses producible by the IPG, inaccordance with the prior art.

FIG. 3 shows use of an External Trial Stimulator (ETS) useable toprovide stimulation before implantation of an IPG, in accordance withthe prior art.

FIG. 4 shows various external devices capable of communicating with andprogramming stimulation in an IPG and ETS, in accordance with the priorart.

FIG. 5 shows a Graphical User Interface (GUI) of a clinician programmerexternal device for setting or adjusting stimulation parameters, inaccordance with the prior art.

FIG. 6 shows sweet spot searching to determine effective electrodes fora patient using a movable sub-perception bipole.

FIGS. 7A-7D show sweet spot searching to determine effective electrodesfor a patient using a movable supra-perception bipole.

FIG. 8 shows stimulation circuitry useable in the IPG or ETS capable ofproviding Multiple Independent Current Control to independently set thecurrent at each of the electrodes.

FIG. 9 shows a flow chart of a study conducted on various patients withback pain designed to determine optimal sub-perception SCS stimulationparameters over a frequency range of 1 kHz to 10 kHz.

FIGS. 10A-10C show various results of the study as a function ofstimulation frequency in the 1 kHz to 10 kHz frequency range, includingaverage optimal pulse width (FIG. 10A), mean charge per second andoptimal stimulation amplitude (FIG. 10B), and back pain scores (FIG.10C).

FIGS. 11A-11C shows further analysis of relationships between averageoptimal pulse width and frequency in the 1 kHz to 10 kHz frequencyrange, and identifies statistically-significant regions of optimizationof these parameters.

FIG. 12A shows results of patients tested with sub-perception therapy atfrequencies at or below 1 kHz, and shows optimal pulse width rangesdetermined at tested frequencies, and optimal pulse width v. frequencyregions for sub-perception therapy.

FIG. 12B shows various modelled relationships between average optimalpulse width and frequency at or below 1 kHz.

FIG. 12C shows the duty of cycle of the optimal pulse widths as afunction of frequencies at or below 1 kHz.

FIG. 12D shows the average battery current and battery discharge time atthe optimal pulse widths as a function of frequencies at or below 1 kHz.

FIG. 13 shows a fitting module showing how the relationships and regionsdetermined relating optimal pulse width and frequency (≤10 kHz) can beused to set sub-perception stimulation parameters for an IPG or ETS.

FIG. 14 shows an algorithm used for supra-perception sweet spotsearching followed by sub-perception therapy, and possible optimizationof the sub-perception therapy using the fitting module.

FIG. 15 shows an alternative algorithm for optimization of thesub-perception therapy using the fitting module.

DETAILED DESCRIPTION

While Spinal Cord Stimulation (SCS) therapy can be an effective means ofalleviating a patient's pain, such stimulation can also causeparesthesia. Paresthesia—sometimes referred to a “supra-perception”therapy—is a sensation such as tingling, prickling, heat, cold, etc.that can accompany SCS therapy. Generally, the effects of paresthesiaare mild, or at least are not overly concerning to a patient. Moreover,paresthesia is generally a reasonable tradeoff for a patient whosechronic pain has now been brought under control by SCS therapy. Somepatients even find paresthesia comfortable and soothing.

Nonetheless, at least for some patients, SCS therapy would ideallyprovide complete pain relief without paresthesia—what is often referredto as “sub-perception” or sub-threshold therapy that a patient cannotfeel. Effective sub-perception therapy may provide pain relief withoutparesthesia by issuing stimulation pulses at higher frequencies.Unfortunately, such higher-frequency stimulation may require more power,which tends to drain the battery 14 of the IPG 10. See, e.g., U.S.Patent Application Publication 2016/0367822. If an IPG's battery 14 is aprimary cell and not rechargeable, high-frequency stimulation means thatthe IPG 10 will need to be replaced more quickly. Alternatively, if anIPG battery 14 is rechargeable, the IPG 10 will need to be charged morefrequently, or for longer periods of time. Either way, the patient isinconvenienced.

In an SCS application, it is desirable to determine a stimulationprogram that will be effective for each patient. A significant part ofdetermining an effective stimulation program is to determine a “sweetspot” for stimulation in each patient, i.e., to select which electrodesshould be active (E) and with what polarities (P) and relativeamplitudes (X %) to recruit and thus treat a neural site at which painoriginates in a patient. Selecting electrodes proximate to this neuralsite of pain can be difficult to determine, and experimentation istypically undertaken to select the best combination of electrodes toprovide a patient's therapy.

As described in U.S. Patent Application Publication 2019/0366104, whichis hereby expressly incorporated by reference, selecting electrodes fora given patient can be even more difficult when sub-perception therapyis used, because the patient does not feel the stimulation, andtherefore it can be difficult for the patient to feel whether thestimulation is “covering” his pain and therefore whether selectedelectrodes are effective. Further, sub-perception stimulation therapymay require a “wash in” period before it can become effective. A wash inperiod can take up to a day or more, and therefore sub-perceptionstimulation may not be immediately effective, making electrode selectionmore difficult.

FIG. 6 briefly explains the '539 application's technique for a sweetspot search, i.e., how electrodes can be selected that are proximate toa neural site of pain 298 in a patient, when sub-perception stimulationis used. The technique of FIG. 6 is particularly useful in a trialsetting after a patient is first implanted with an electrode array,i.e., after receiving their IPG or ETS.

In the example shown, it is assumed that a pain site 298 is likelywithin a tissue region 299. Such region 299 may be deduced by aclinician based on the patient symptoms, e.g., by understanding whichelectrodes are proximate to certain vertebrae (not shown), such aswithin the T9-T10 interspace. In the example shown, region 299 isbounded by electrodes E2, E7, E15, and E10, meaning that electrodesoutside of this region (e.g., E1, E8, E9, E16) are unlikely to have aneffect on the patient's symptoms. Therefore, these electrodes may not beselected during the sweet spot search depicted in FIG. 6, as explainedfurther below.

In FIG. 6, a sub-perception bipole 297 a is selected, in which oneelectrode (e.g., E2) is selected as an anode that will source a positivecurrent (+A) to the patient's tissue, while another electrode (e.g., E3)is selected as a cathode that will sink a negative current (−A) from thetissue. This is similar to what was illustrated earlier with respect toFIG. 2, and biphasic stimulation pulses can be used employing activecharge recovery. Because the bipole 297 a provides sub-perceptionstimulation, the amplitude A used during the sweet spot search istitrated down until the patient no longer feels paresthesia. Thissub-perception bipole 297 a is provided to the patient for a duration,such as a few days, which allows the sub-perception bipole's potentialeffectiveness to “wash in,” and allows the patient to provide feedbackconcerning how well the bipole 297 a is helping their symptoms. Suchpatient feedback can comprise a pain scale ranking. For example, thepatient can rank their pain on a scale from 1-10 using a NumericalRating Scale (NRS) or the Visual Analogue Scale (VAS), with 1 denotingno or little pain and 10 denoting a worst pain imaginable. As discussedin the '539 application, such pain scale ranking can be entered into thepatient's external controller 45.

After the bipole 297 a is tested at this first location, a differentcombination of electrodes is chosen (anode electrode E3, cathodeelectrode E4), which moves the location of the bipole 297 in thepatient's tissue. Again, the amplitude of the current A may need to betitrated to an appropriate sub-perception level. In the example shown,the bipole 297 a is moved down one electrode lead, and up the other, asshown by path 296 in the hope of finding a combination of electrodesthat covers the pain site 298. In the example of FIG. 6, given the painsite 298's proximity to electrodes E13 and E14, it might be expectedthat a bipole 297 a at those electrodes will provide the best relief forthe patient, as reflected by the patient's pain score rankings. Theparticular stimulation parameters chosen when forming bipole 297 a canbe selected at the GUI 64 of the clinician programmer 50 or otherexternal device (such as a patient external controller 45) andwirelessly telemetered to the patient's IPG or ETS for execution.

While the sweet spot search of FIG. 6 can be effective, it can also takea significantly long time when sub-perception stimulation is used. Asnoted, sub-perception stimulation is provided at each bipole 297location for a number of days, and because a large number of bipolelocations are chosen, the entire sweep spot search can take up to amonth to complete.

The inventors have determined via testing of SCS patients that even ifit is desired to eventually use sub-perception therapy for a patientgoing forward after the sweet spot search, it is beneficial to usesupra-perception stimulation during the sweet spot search to selectactive electrodes for the patient. Use of supra-perception stimulationduring the sweet spot search greatly accelerates determination ofeffective electrodes for the patient compared to the use ofsub-perception stimulation, which requires a wash in period at each setof electrodes tested. After determining electrodes for use with thepatient using supra-perception therapy, therapy may be titrated tosub-perception levels keeping the same electrodes determined for thepatient during the sweet spot search. Because the selected electrodesare known to be recruiting the neural site of the patient's pain, theapplication of sub-perception therapy to those electrodes is more likelyto have immediate effect, reducing or potentially eliminating the needto wash in the sub-perception therapy that follows. In short, effectivesub-perception therapy can be achieved more quickly for the patient whensupra-perception sweet spot searching is utilized. Preferably,supra-perception sweet spot searching occurs using symmetric biphasicpulses occurring at low frequencies—such as between 40 and 200 Hz in oneexample.

In accordance with one aspect of the disclosed technique, a patient willbe provided sub-perception therapy. Sweet spot searching to determineelectrodes that may be used during sub-perception therapy may precedesuch sub-perception therapy. In some aspects, when sub-perceptiontherapy is used for the patient, sweet spot searching may use a bipole297 a that is sub-perception (FIG. 6), as just described. This may berelevant because the sub-perception sweet spot search may match theeventual sub-perception therapy the patient will receive.

However, the inventors have determined that even if sub-perceptiontherapy is eventually to be used for the patient, it can be beneficialto use supra-perception stimulation—that is, stimulation withaccompanying paresthesia—during the sweet spot search. This is shown inFIG. 7A, where the movable bipole 301 a provides supra-perceptionstimulation that can be felt by the patient. Providing bipole 301 a assupra-perception stimulation can merely involve increasing its amplitude(e.g., current A) when compared to the sub-perception bipole 297 a ofFIG. 6, although other stimulation parameters might be adjusted as well,such as by providing longer pulse widths.

The inventors have determined that there are benefits to employingsupra-perception stimulation during the sweet spot search even thoughsub-perception therapy will eventually be used for the patient.

First, as mentioned above, the use of supra-perception therapy bydefinition allows the patient to feel the stimulation, which enables thepatient to provide essentially immediate feedback to the clinicianwhether the paresthesia seems to be well covering his pain site 298. Inother words, it is not necessary to take the time to wash in bipole 301a at each location as it is moved along path 296. Thus, a suitablebipole 301 a proximate to the patient's pain site 298 can be establishedmuch more quickly, such as within a single clinician's visit, ratherthan over a period of days or weeks. In one example, when sub-perceptiontherapy is preceded with supra-perception sweet spot searching, the timeneeded to wash in the sub-perception therapy can be one hour or less,ten minutes or less, or even a matter of seconds. This allows wash in tooccur during a single programming session during which the patient's IPGor ETS is programmed, and without the need for the patient to leave theclinician's office.

Second, use of supra-perception stimulation during the sweet spot searchensures that electrodes are determined that well recruit the pain site298. As a result, after the sweet spot search is complete and eventualsub-perception therapy is titrated for the patient, wash in of thatsub-perception therapy may not take as long because the electrodesneeded for good recruitment have already been confidently determined.

FIGS. 7B-7D show other supra-perception bipoles 301 b-301 d that may beused, and in particular show how the virtual bipoles may be formed usingvirtual poles by activating three or more of the electrodes 16. Virtualpoles are discussed further in U.S. Patent Application Publication2019/0175915, which is incorporated herein by reference in its entirety,and thus virtual poles are only briefly explained here. Forming virtualpoles is assisted if the stimulation circuitry 28 or 44 used in the IPGor ETS is capable of independently setting the current at any of theelectrodes—what is sometimes known as a Multiple Independent CurrentControl (MICC), which is explained further below with reference to FIG.8.

When a virtual bipole is used, the GUI 64 (FIG. 5) of the clinicianprogrammer 50 (FIG. 4) can be used to define an anode pole (+) and acathode pole (−) at positions 291 (FIG. 7B) that may not necessarilycorrespond to the position of the physical electrodes 16. The controlcircuitry 70 in the clinician programmer 50 can compute from thesepositions 291 and from other tissue modeling information which physicalelectrodes 16 will need to be selected and with what amplitudes to formthe virtual anode and virtual cathode at the designated positions 291.As described earlier, amplitudes at selected electrodes may be expressedas a percentage X % of the total current amplitude A specified at theGUI 64 of the clinician programmer 50.

For example, in FIG. 7B, the virtual anode pole is located at a position291 between electrodes E2, E3 and E10. The clinician programmer 50 maythen calculate based on this position that each of these electrodes(during first pulse phase 30 a) will receive an appropriate share (X %)of the total anodic current+A to locate the virtual anode at thisposition. Since the virtual anode's position is closest to electrode E2,this electrode E2 may receive the largest share of the specified anodiccurrent+A (e.g., 75%*+A). Electrodes E3 and E10 which are proximate tothe virtual anode pole's position but farther away receive lesser sharesof the anodic current (e.g., 15%*+A and 10%*+A respectively). Likewise,it can be seen that from the designated position 291 of the virtualcathode pole, which is proximate to electrodes E4, E11, and E12, thatthese electrodes will receive an appropriate share of the specifiedcathodic current −A (e.g., 20%*-A, 20%*-A, and 60%*-A respectively,again during the first pulse phase 30 a). These polarities would then beflipped during the second phases 30 b of the pulses, as shown in thewaveforms of FIG. 7B. In any event, the use of virtual poles in theformation of bipole 301 b allows the field in the tissue to be shaped,and many different combinations of electrodes can be tried during thesweet spot search. In this regard, it is not strictly necessary that the(virtual) bipole be moved along an orderly path 296 with respect to theelectrodes, and the path may be randomized, perhaps as guided byfeedback from the patient.

FIG. 7C shows a useful virtual bipole 301 c configuration that can beused during the sweet spot search. This virtual bipole 301 c againdefines a target anode and cathode whose positions do not correspond tothe position of the physical electrodes. The virtual bipole 301 c isformed along a lead—essentially spanning the length of four electrodesfrom E1 to E5. This creates a larger field in the tissue better able torecruit the patient's pain site 298. This bipole configuration 301 c mayneed to be moved to a smaller number of locations than would a smallerbipole configuration compared 301 a of FIG. 7A) as it moves along path296, thus accelerating pain site 298 detection. FIG. 7D expands upon thebipole configuration of FIG. 7C to create a virtual bipole 301 d usingelectrodes formed on both leads, e.g., from electrodes E1 to E5 and fromelectrodes E9 to E13. This bipole 301 d configuration need only be movedalong a single path 296 that is parallel to the leads, as its field islarge enough to recruit neural tissue proximate to both leads. This canfurther accelerate pain site detection.

In some aspects, the supra-perception bipoles 301 a-301 d used duringthe sweet spot search comprise symmetric biphasic waveforms havingactively-driven (e.g., by the stimulation circuitry 28 or 44) pulsephases 30 a and 30 b of the same pulse width PW and the same amplitude(with the polarity flipped during the phases) (e.g., A_(30a)=A_(30b),and PW_(30a)=PW_(30b)). This is beneficial because the second pulsephase 30 b provides active charge recovery, with in this case the chargeprovided during the first pulse phase 30 a (Q_(30a)) equaling the chargeof the second pulse phase 30 b (Q_(30b)), such that the pulses arecharge balanced. Use of biphasic waveforms are also believed beneficialbecause, as is known, the cathode is largely involved in neural tissuerecruitment. When a biphasic pulse is used, the positions of the(virtual) anode and cathode will flip during the pulse's two phases.This effectively doubles the neural tissue that is recruited forstimulation, and thus increases the possibility that the pain site 298will be covered by a bipole at the correct location.

The supra-perception bipoles 301 a-301 d do not however need to comprisesymmetric biphasic pulses as just described. For example, the amplitudeand pulse width of the two phases 30 a and 30 b can be different, whilekeeping the charge (Q) of the two phases balanced (e.g.,Q_(30a)=A_(30a)*PW_(30a)=A_(30b)*PW_(30b)=Q_(30b)). Alternatively, thetwo phases 30 a and 30 b may be charge imbalanced (e.g.,Q_(30a)=A_(30a)*PW_(30a)>A_(30b)*PW_(30b)=Q_(30b), orQ_(30a)=A_(30a)*PW_(30a)<A_(30b)*PW_(30b)=Q_(30b)). In short, the pulsesin bipoles 301-301 d can be biphasic symmetric (and thus inherentlycharge balanced), biphasic asymmetric but still charge balanced, orbiphasic asymmetric and charge imbalanced.

In a preferred example, the frequency F of the supra-perception pulses301 a-301 d used during the supra-perception sweet spot search may be 10kHz or less, 1 kHz or less, 500 Hz or less, 300 Hz or less, 200 Hz orless, 130 Hz or less, or 100 Hz or less, or ranges bounded by two ofthese frequencies (e.g., 100-130 Hz, or 100-200 Hz). In particularexamples, frequencies of 90 Hz, 40 Hz, or 10 Hz can be used, with pulsescomprising biphasic pulses which are preferably symmetric. However, asingle actively-driven pulse phase followed by a passive recovery phasecould also be used. The pulse width PW may also comprise a value in therange of hundreds of microseconds, such as 150 to 400 microseconds.Because the goal of supra-perception sweet spot searching is merely todetermine electrodes that appropriately cover a patient's pain,frequency and pulse width may be of less importance at this stage. Onceelectrodes have been chosen for sub-perception stimulation, frequencyand pulse width can be optimized, as discussed further below.

It should be understood that the supra-perception bipoles 301 a-301 dused during sweet spot searching need not necessarily be the sameelectrodes that are selected when later providing the patient withsub-perception therapy. Instead, the best location of the bipole noticedduring the search can be used as the basis to modify the selectedelectrodes. Suppose for example that a bipole 301 a (FIG. 7A) is usedduring sweep spot searching, and it is determined that bipole providesthe best pain relief when located at electrodes E13 and E14. At thatpoint, sub-perception therapy using those electrodes E13 and E14 can betried for the patient going forward. Alternatively, it may be sensibleto modify the selected electrodes to see if the patient's symptoms canbe further improved before sub-perception therapy is tried. For example,the distance (focus) between the cathode and anode can be varied, usingvirtual poles as already described. Or, a tripole (anode/cathode/anode)consisting of electrodes E12/E13/E14 or E13/E14/E15 could be tried. SeeU.S. Patent Application Publication 2019/0175915 (discussing tripoles).Or electrodes on a different lead could also be tried in combinationwith E13 and E14. For example, because electrodes E5 and E6 aregenerally proximate to electrodes E13 and E14, it may be useful to addE5 or E6 as sources of anodic or cathodic current (again creatingvirtual poles). All of these types of adjustments should be understoodas comprising “steering” or an adjustment to the “location” at whichtherapy is applied, even if a central point of stimulation doesn'tchange (as can occur for example when the distance or focus between thecathode and anode is varied).

Multiple Independent Current Control (MICC) is explained in one examplewith reference to FIG. 8, which shows the stimulation circuitry 28(FIG. 1) or 44 (FIG. 3) in the IPG or ETS used to form prescribedstimulation at a patient's tissue. The stimulation circuitry 28 or 44can control the current or charge at each electrode independently, andusing GUI 64 (FIG. 5) allows the current or charge to be steered todifferent electrodes, which is useful for example when moving the bipole301 i along path 296 during the sweet spot search (FIG. 7A-7D). Thestimulation circuitry 28 or 44 includes one or more current sources 440_(i) and one or more current sinks 442 k. The sources and sinks 440 _(i)and 442 _(i) can comprise Digital-to-Analog converters (DACs), and maybe referred to as PDACs 440 _(i) and NDACs 442 _(i) in accordance withthe Positive (sourced, anodic) and Negative (sunk, cathodic) currentsthey respectively issue. In the example shown, a NDAC/PDAC 440 _(i)/442_(i) pair is dedicated (hardwired) to a particular electrode node ei 39.Each electrode node ei 39 is preferably connected to an electrode Ei 16via a DC-blocking capacitor Ci 38, which act as a safety measure toprevent DC current injection into the patient, as could occur forexample if there is a circuit fault in the stimulation circuitry 28 or44. PDACs 440 _(i) and NDACs 442 _(i) can also comprise voltage sources.

Proper control of the PDACs 440 _(i) and NDACs 442 _(i) via GUI 64allows any of the electrodes 16 and the case electrode Ec 12 to act asanodes or cathodes to create a current through a patient's tissue. Suchcontrol preferably comes in the form of digital signals Tip and Iin thatset the anodic and cathodic current at each electrode Ei. If for exampleit is desired to set electrode E1 as an anode with a current of +3 mA,and to set electrodes E2 and E3 as cathodes with a current of −1.5 mAeach, control signal Ilp would be set to the digital equivalent of 3 mAto cause PDAC 440 ₁ to produce+3 mA, and control signals I2 n and I3 nwould be set to the digital equivalent of 1.5 mA to cause NDACs 442 ₂and 442 ₃ to each produce −1.5 mA. Note that definition of these controlsignals can also occur using the programmed amplitude A and percentage X% set in the GUI 64. For example, A may be set to 3 mA, with E1designated as an anode with X=100%, and with E2 and E3 designated atcathodes with X=50%. Alternatively, the control signals may not be setwith a percentage, and instead the GUI 64 can simply prescribe thecurrent that will appear at each electrode at any point in time.

In short, the GUI 64 may be used to independently set the current ateach electrode, or to steer the current between different electrodes.This is particularly useful in forming virtual bipoles, which asexplained earlier involve activation of more than two electrodes. MICCalso allows more sophisticated electric fields to be formed in thepatient's tissue.

Other stimulation circuitries 28 can also be used to implement MICC. Inan example not shown, a switching matrix can intervene between the oneor more PDACs 440 _(i) and the electrode nodes ei 39, and between theone or more NDACs 442 _(i) and the electrode nodes. Switching matricesallows one or more of the PDACs or one or more of the NDACs to beconnected to one or more electrode nodes at a given time. Variousexamples of stimulation circuitries can be found in U.S. Pat. Nos.6,181,969, 8,606,362, 8,620,436, and U.S. Patent ApplicationPublications 2018/0071513, 2018/0071520, and 2019/0083796.

Much of the stimulation circuitry 28 or 44, including the PDACs 440 iand NDACs 442 i, the switch matrices (if present), and the electrodenodes ei 39 can be integrated on one or more Application SpecificIntegrated Circuits (ASICs), as described in U.S. Patent ApplicationPublications 2012/0095529, 2012/0092031, and 2012/0095519. As explainedin these references, ASIC(s) may also contain other circuitry useful inthe IPG 10, such as telemetry circuitry (for interfacing off chip withthe IPG' s or ETS's telemetry antennas), circuitry for generating thecompliance voltage VH that powers the stimulation circuitry, variousmeasurement circuits, etc.

While it is preferred to use sweet spot searching, and in particularsupra-perception sweet spot searching, to determine the electrodes to beused during subsequent sub-perception therapy, it should be noted thatthis is not strictly necessary. Sub-perception therapy can be precededby sub-perception sweet spot searching, or may not be preceded by sweetspot searching at all. In short, sub-perception therapy as describednext is not reliant on the use of any sweet spot search.

In another aspect of the invention, the inventors have determined viatesting of SCS patients that statistically significant correlationsexists between pulse width (PW) and frequency (F) where an SCS patientwill experience a reduction in back pain without paresthesia(sub-perception). Use of this information can be helpful in decidingwhat pulse width is likely optimal for a given SCS patient based on aparticular frequency, and in deciding what frequency is likely optimalfor a given SCS patient based on a particular pulse width. Beneficially,this information suggests that paresthesia-free sub-perception SCSstimulation can occur at frequencies of 10 kHz and below. Use of suchlow frequencies allows sub-perception therapy to be used with much lowerpower consumption in the patient's IPG or ETS.

FIGS. 9-11C shows results derived from testing patients at frequencieswithin a range of 1 kHz to 10 kHz. FIG. 9 explains how data was gatheredfrom actual SCS patients, and the criteria for patient inclusion in thestudy. Patients with back pain, but not yet receiving SCS therapy, werefirst identified. Key patient inclusion criteria included havingpersistent lower back pain for greater than 90 days; a NRS pain scale of5 or greater (NRS is explained below); stable opioid medications for 30days; and a Baseline Oswestry Disability index score of greater than orequal to 20 and lower than or equal to 80. Key patient exclusioncriteria included having back surgery in the previous 6 months;existence of other confounding medical/psychological conditions; anduntreated major psychiatric comorbidity or serious drug related behaviorissues.

After such initial screening, patients periodically entered aqualitative indication of their pain (i.e., a pain score) into aportable e-diary device, which can comprise a patient externalcontroller 45, and which in turn can communicate its data to a clinicianprogrammer 50 (FIG. 4). Such pain scores can comprise a Numerical RatingScale (NRS) score from 1-10, and were input to the e-diary three timesdaily. As shown in FIG. 10C, the baseline NRS score for patients noteventually excluded from the study and not yet receiving sub-perceptionstimulation therapy was approximately 6.75/10, with a standard error, SE(sigma/SQRT(n)) of 0.25.

Returning to FIG. 9, patients then had trial leads 15′ (FIG. 3)implanted on the left and right sides of the spinal column, and wereprovided external trial stimulation as explained earlier. A clinicianprogrammer 50 was used to provide a stimulation program to eachpatient's ETS 40 as explained earlier. This was done to make sure thatSCS therapy was helpful for a given patient to alleviate their pain. IfSCS therapy was not helpful for a given patient, trial leads 15′ wereexplanted, and that patient was then excluded from the study.

Those patients for whom external trial stimulation was helpfuleventually received full implantation of a permanent IPG 10, asdescribed earlier. After a healing period, and again using clinicianprogrammer 50, a “sweet spot” for stimulation was located in eachpatient, i.e., which electrodes should be active (E) and with whatpolarities (P) and relative amplitudes (X %) to recruit and thus treat asite 298 of neural site in the patient. The sweet spot search can occurin any of the manners described earlier with respect to FIGS. 6-7D, butin a preferred embodiment would comprise supra-perception stimulation(e.g., e.g., 7A-7D) because of the benefits described earlier. However,this is not strictly necessary, and sub-perception stimulation can alsobe used during the sweet spot search. In the example of FIG. 9, sweetspot searching occurred at 10 kHz, but again the frequency used duringthe sweet spot search can be varied. Symmetric biphasic pulses were usedduring sweet spot searching, but again, this is not strictly required.Deciding which electrodes should be active started with selectingelectrodes 16 present between thoracic vertebrae T9 and T10. However,electrodes as far away as T8 and T11 were also activated if necessary.Which electrodes were proximate to vertebrae T8, T9, T10, and T1 wasdetermined using fluoroscopic images of the leads 15 within eachpatient.

During sweet spot searching, bipolar stimulation using only twoelectrodes was used for each patient, and using only adjacent electrodeson a single lead 15, similar to what was described in FIGS. 6 and 7A.Thus, one patient's sweet spot might involve stimulating adjacentelectrodes E4 as cathode and E5 as anode on the left lead 15 as shownearlier in FIG. 2 (which electrodes may be between T9 and T10), whileanother patient's sweet spot might involve stimulating adjacentelectrodes E9 as anode and E10 as cathode on the right lead 15 (whichelectrodes may be between T10 and T11). Using only adjacent-electrodebipolar stimulation and only between vertebrae T8 to T11 was desired tominimize variance in the therapy and pathology between the differentpatients in the study. However, more complicated bipoles such as thosedescribed with respect to FIGS. 7B-7D could also be used during sweetspot searching. If a patient had sweet spot electrodes in the desiredthoracic location, and if they experienced a 30% or greater pain reliefper an NRS score, such patients were continued in the study; patientsnot meeting these criteria were excluded from further study. While thestudy started initially with 39 patients, 19 patients were excluded fromstudy up to this point in FIG. 9, leaving a total of 20 patientsremaining.

The remaining 20 patients were then subjected to a “washout” period,meaning their IPGs did not provide stimulation for a time. Specifically,patients' NRS pain scores were monitored until their pain reached 80% oftheir initial baseline pain. This was to ensure that previous benefitsof stimulation did not carry over to a next analysis period.

Thereafter, remaining patients were subjected to sub-perception SCStherapy at different frequencies in the range from 1 kHz to 10 kHz usingthe sweet spot active electrodes determined earlier. This however isn'tstrictly necessary, because as noted earlier the current at eachelectrode could also be independently controlled to assist in shaping ofthe electric filed in the tissue. As shown in FIG. 9, the patients wereeach tested using stimulation pulses with frequencies of 10 kHz, 7 kHz,4 kHz, and 1 kHz. FIG. 9 for simplicity shows that these frequencieswere tested in this order for each patient, but in reality thefrequencies were applied to each patient in random orders. Testing at agiven frequency, once complete, was followed by a washout period beforetesting at another frequency began.

At each tested frequency, the amplitude (A) and pulse width (PW) (firstpulse phase 30 a; FIG. 2) of the stimulation was adjusted and optimizedfor each patient such that each patient experienced good pain reliefpossible but without paresthesia (sub-perception). Specifically, usingclinician programmer 50, and keeping as active the same sweet spotelectrodes determined earlier (although again this isn't strictlynecessary), each patient was stimulated at a low amplitude (e.g., 0),which amplitude was increased to a maximum point (perception threshold)where paresthesia was noticeable by the patient. Initial stimulation wasthen chosen for the patient at 50% of that maximum amplitude, i.e., suchthat stimulation was sub-perception and hence paresthesia free. However,other percentages of the maximum amplitude (80%, 90%, etc.) could bechosen as well, and can vary with patient activity or position, asexplained further below. In one example, the stimulation circuitry 28 or44 in the IPG or ETS is configurable to receive an instruction from theGUI 64 via a selectable option (not shown) to reduce the amplitude ofthe stimulation pulses to or by a set amount or percentage to render theso that the pulses can be made sub-perception if they are not already.Other stimulation parameters may also be reduced (e.g., pulse width,charge) to the same effect.

The patient would then leave the clinician's office, and thereafter andin communication with the clinician (or her technician or programmer)would make adjustments to his stimulation (amplitude and pulse width)using his external controller 45 (FIG. 4). At the same time, the patientwould enter NRS pain scores in his e-diary (e.g., the externalcontroller), again three times a day. Patient adjustment of theamplitude and pulse width was typically an iterative process, butessentially adjustments were attempted based on feedback from thepatient to adjust the therapy to decrease their pain while stillensuring that stimulation was sub-perception. Testing at each frequencylasted about three weeks, and stimulation adjustments might be madeevery couple of days or so. At the end of the testing period at a givenfrequency, optimal amplitude and pulse widths had been determined andwere logged for each patient, along with patient NRS pain scores forthose optimal parameters as entered in their e-diaries.

In one example, the percentage of the maximum amplitude used to providesub-perception stimulation could be chosen dependent on an activitylevel or position of the patient. In regard, the IPG or ETS can includemeans for determining patient activity or position, such as anaccelerometer. If the accelerometer indicates a high degree of patientactivity or a position where the electrodes would be farther away fromthe spinal cord (e.g., lying down), the amplitude could be increased toa higher percentage to increase the current (e.g., 90% of the maximumamplitude). If the patient is experiencing a lower degree of activity ora position where the electrodes would be closer to the spinal card(e.g., standing), the amplitude can be decreased (e.g., to 50% of themaximum amplitude). Although not shown, the GUI 64 of the externaldevice (FIG. 5) can include an option to set the percentage of themaximum amplitude at which paresthesia become noticeable to the patient,thus allowing the patient to adjust the sub-perception currentamplitude.

Preferably, Multiple Independent Current Control (MICC) is used toprovide or adjust the sub-perception therapy, as discussed earlier withreference to FIG. 8. This allows the current at each electrode to beindependently set, which promotes the steering of current or chargebetween electrodes, facilitates the formation of virtual bipoles, andmore generally allows the electric field to be shaped in the patient'stissue. In particular, MICC, can be used to steer sub-perception therapyto different locations in the electrode array and thus the spinal cord.For example, once a set of sub-perception stimulation parameters hasbeen chosen for the patient, one or more of the stimulation parameterscan be changed. Such changes may be warranted or dictated by the therapylocation. The physiology of the patient may vary at different vertebralpositions, and tissue may be more or less conductive at differenttherapy locations. Therefore, if the sub-perception therapy location issteered to a new location along the spinal cord (which location changemay comprise changing the anode/cathode distance or focus), it may bewarranted to adjust at least one of the stimulation parameters, such asamplitude. As noted earlier, making sub-perception adjustment isfacilitated, and can occur within a programming session, because asubstantial wash in period may not be necessary.

Adjustment to sub-perception therapy can also include varying otherstimulation parameters, such as pulse width, frequency, and even theduration of the interphase period (IP) (FIG. 2). The interphase durationcan impact the neural dose, or the rate of charge infusion, such thathigher sub-perception amplitudes would be used with shorter interphasedurations. In one example, the interphase duration can be varied between0-3 ms. After a washout period, a new frequency was tested, using thesame protocol as just described.

The sub-perception stimulation pulses used were symmetric biphasicconstant current amplitude pulses, having first and second pulses phases30 a and 30 b with the same duration (see FIG. 2). However, constantvoltage amplitude pulses could be used as well. Pulses of differentshapes (triangles, sine waves, etc.) could also be used.Pre-pulsing—that is, providing a small current prior to providing theactively-driven pulse phase(s)—to affect polarization or depolarizationof neural tissue can also occur when providing sub-perception therapy.See, e.g., U.S. Pat. No. 9,008,790, which is incorporated herein byreference.

FIGS. 10A-10C show the results of testing the patients at 10 kHz, 7 kHz,4 Hz and 1 kHz. Data is shown in each figure as average values for the20 remaining patients at each frequency, with error bars reflectingstandard error (SE) between the patients.

Starting with FIG. 10B, the optimized amplitude A for the 20 remainingpatients are shown at the tested frequencies. Interestingly, the optimalamplitude at each frequency was essentially constant—around 3 mA. FIG.10B also shows the amount of energy expended at each frequency, morespecifically a mean charge per second (MCS) (in mC/s) attributable tothe pulses. MCS is computed by taking the optimal pulse width (FIG. 10A,discussed next) and multiplying it by the optimal amplitude (A) and thefrequency (F), which MCS value can comprise a neural dose. MCScorrelates to the current or power that the battery in the IPG 10 mustexpend to form the optimal pulses. Significantly, the MCS issignificantly lower at lower frequencies: for example, the MCS at F=1kHz is approximately ⅓ of its value at higher frequencies (e.g., F=7 kHzor 10 kHz). This means that optimal SCS therapy—that alleviates backpain without paresthesia—is achievable at lower frequencies like F=1kHz, with the added benefit of lower power draws that are moreconsiderate of the IPG 10's (or ETS 40's) battery.

FIG. 10A shows optimal pulse width as a function of frequency for the 1kHz to 10 kHz frequency range tested. As shown, the relationship followsa statistically significant trend: when modeled using linear regression98 a, PW=−8.22F+106, where pulse width is measured in microseconds andfrequency is measured in kiloHertz, with a correlation coefficient R² of0.974; when modeled using polynomial regression 98 b,PW=0.486F²−13.6F+116, again with pulse width measured in microsecondsand frequency measured in kiloHertz, with an even better correlationcoefficient of R²=0.998. Other fitting methods could be used toestablish other information relating frequency and pulse width at whichstimulation pulses are formed to provide pain relief without paresthesiain the frequency range of 1 kHz to 10 kHz.

Note that the relationship between optimal pulse width and frequency isnot simply an expected relationship between frequency and duty cycle(DC), i.e., the duration that a pulse is ‘on’ divided by its period(1/F). In this regard, notice that a given frequency has a naturaleffect on pulse width: one would expect that a higher frequency pulseswould have smaller pulse widths. Thus, it might be expected for examplethat a 1 kHz waveform with a 100 microsecond pulse width would have thesame clinical results as a 10 kHz waveform with a 10 microsecondfrequency, because the duty cycle of both of these waveforms is 10%.FIG. 11A shows the resulting duty cycle of the stimulation waveformsusing the optimal pulse width in the frequency range of 1 kHz to 10 kHz.Here, duty cycle is computed by considering the total ‘on’ time of thefirst pulse phase 30 a (FIG. 2) only; the duration of the symmetricsecond pulse phase is ignored. This duty cycle is not constant over the1 kHz to 10 kHz frequency range: for example, the optimal pulse width at1 kHz (104 microseconds) is not merely ten times the optimal pulse widthat 10 kHz (28.5 microseconds). Thus, there is significance to theoptimal pulse widths beyond a mere scaling of the frequency.

FIG. 10C shows average patient pain scores at the optimal stimulationparameters (optimal amplitude (FIG. 7B) and pulse width (FIG. 7A)) foreach frequency in the range of 1 kHz to 10 kHz. As noted earlier,patients in the study, prior to receiving SCS therapy, initiallyreported pain scores with an average of 6.75. After SCS implantation andduring the study, and with amplitude and pulse width optimized duringthe provisional of sub-perception therapy, their average pain scoresdropped significantly, to an average score of about 3 for allfrequencies tested.

FIG. 11A provides a deeper analysis of the resulting relationshipbetween optimal pulse width and frequency in the frequency range of 1kHz to 10 kHz. The chart in FIG. 11A shows the average optimal pulsewidth for the 20 patients in the study at each frequency, along with thestandard error resulting from variations between them. These arenormalized at each frequency by dividing the standard error by theoptimal pulse width, ranging in variations at each frequency between5.26% and 8.51%. From this, a 5% variance (lower than all computedvalues) can be assumed as a statistically-significant variance at allfrequencies tested.

From this 5% variance, a maximum average pulse width (PW+5%) and aminimum average pulse width (PW+5%) can be calculated for eachfrequency. For example, the optimal average pulse width PW at 1 kHz is104 microseconds, and 5% above this value (1.05*104 μs) is 109 μs; 5%below this value (0.95*104) is 98.3 μs. Likewise, the optimal averagepulse width AVG(PW) at 4 kHz is 68.0 microseconds, and 5% above thisvalue (1.05*68.0 μs) is 71.4 μs; 5% below this value (0.95*68.0 μs) is64.6 μs. Thus, a statistically-significant reduction in pain withoutparesthesia occurs in or on the linearly bounded region 100 a of points102 of (1 kHz, 98.3 μs), (1 kHz, 109 μs), (4 kHz, 71.4 μs), and (4 kHz,64.6 μs). A linearly bounded region 100 b around points 102 is alsodefined for frequencies greater than or equal to 4 kHz and less than orequal to 7 kHz: (4 kHz, 71.4 μs), (4 kHz, 64.6 μs), (7 kHz, 44.2 μs), (7kHz, 48.8 μs). A linear bounded region 100 c around points 102 is alsodefined for frequencies greater than or equal to 7 kHz and less than orequal to 10 kHz: (7 kHz, 44.2 μs), (7 kHz, 48.8 μs), (10 kHz, 29.9 μs),(10 kHz, 27.1 μs). Such regions 100 thus comprise information relatingfrequency and pulse width at which stimulation pulses are formed toprovide pain relief without paresthesia in the frequency range of 1 kHzto 10 kHz.

FIG. 11B provides an alternative analysis of the resulting relationshipbetween optimal pulse width and frequency. In this example, regions 100a-100 c are defined based upon the standard error (SE) calculated ateach frequency. Thus, points 102 defining the corners of the regions 100a-c are simply located at the extent of the SE error bars at eachfrequency (PW+SE, and PW−SE), even though these error bars are ofdifferent magnitudes at each frequency. Thus, astatistically-significant reduction in pain without paresthesia occursin or on the linearly bounded region 100 a of points (1 kHz, 96.3 μs),(1 kHz, 112 μs), (4 kHz, 73.8 μs), and (4 kHz, 62.2 μs). The linearbounded regions 100 b and 100 c are similar, and because the points 102defining them are set forth in chart at the top of FIG. 11B, they arenot repeated here.

FIG. 11C provides another analysis of the resulting relationship betweenoptimal pulse width and frequency. In this example, regions 100 a-100 care defined based upon the standard deviation (SD) calculated at eachfrequency, which is larger than the standard error (SE) metric used tothis point. Points 102 defining the corners of the regions 100 a-c arelocated at the extent of the SD error bars at each frequency (PW+SD, andPW−SD), although points 102 could also be set within the error bars,similar to what was illustrated earlier with respect to FIG. 11A. In anyevent, a statistically-significant reduction in pain without paresthesiaoccurs in or on the linearly bounded region 100 a of points (1 kHz, 69.6μs), (1 kHz, 138.4 μs), (4 kHz, 93.9 μs), and (4 kHz, 42.1 μs). Thelinear bounded regions 100 b and 100 c are similar, and because thepoints 102 defining them are set forth in chart at the top of FIG. 11C,they are not repeated here.

More generally, although not illustrated, regions within the frequencyrange of 1 kHz to 10 kHz where sub-perception efficacy was achievedcomprises linearly-bounded region 100 a (1 kHz, 50.0 μs), (1 kHz, 200.0μs), (4 kHz, 110.0 μs), and (4 kHz, 30.0 μs); and/or linearly-boundedregion 100 b (4 kHz, 110.0 μs), (4 kHz, 30.0 μs), (7 kHz, 30.0 μs), and(7 kHz, 60.0 μs); and/or linearly-bounded region 100 c (7 kHz, 30.0 μs),(7 kHz, 60.0 μs), (10 kHz, 40.0 μs), and (10 kHz, 20.0 μs).

In summary, one or more statistically-significant regions 100 can bedefined for the optimal pulse width and frequency data taken for thepatients in the study to arrive at combinations of pulse width andfrequency that reduce pain without the side effect of paresthesia withinthe frequency range of 1 kHz to 10 kHz, and different statisticalmeasures of error can be used to so define the one or more regions.

FIGS. 12A-12D show the results of testing other patients withsub-perception stimulation therapy at frequencies at or below 1 kHz.Testing of the patients generally occurred after supra-perception sweepspot searching occurred to select appropriate electrodes (E), polarities(P) and relative amplitudes (X %) for each patient (see FIGS. 7A-7D),although again the sub-perception electrodes used could vary from thoseused during the supra-perception sweet spot search (e.g., using MICC).Patients were tested with sub-perception stimulation using symmetricbiphasic bipoles, although the form of pulses used during sub-perceptiontherapy could vary.

FIG. 12A shows the relationship between frequency and pulse width atwhich effective sub-perception therapy was reported by patients forfrequencies of 1 kHz and below. Note that the same patient selection andtesting criteria described earlier (FIG. 9) can be used when evaluatingfrequencies at or below 1 kHz, with the frequencies adjusted asappropriate.

As can be seen, at each frequency tested, the optimal pulse width againfell within a range. For example, at 800 Hz, patients reported goodresults when the pulse width fell within a range of 105-175microseconds. The upper end of the pulse width range at each frequencyis denoted PW(high), while the lower end of the pulse width range ateach frequency is denoted PW(low). PW(middle) denotes the middle (e.g.,average) of the PW(high) and PW(low) at each frequency. At each of thetested frequencies the amplitude of the current provided (A) wastitrated down to sub-perception levels, such that the patient could notfeel paresthesia. Typically, the current was titrated to 80% of thethreshold at which paresthesia could be sensed. Because each patient'sanatomy is unique, the sub-perception amplitude A could vary frompatient to patient. The pulse width data depicted comprises the pulsewidth of only the first phase of the stimulation pulses.

Table 1 below expresses the optimal pulse width versus frequency data ofFIG. 12A in tabular form for frequencies at or below 1 kHz, with thepulse widths expressed in microseconds:

TABLE 1 Frequency PW(low) PW(middle) PW(high) (Hz) (μs) (μs) (μs) 100090 120 150 800 105 140 175 600 120 160 200 400 140 183 225 200 160 210260 100 195 260 325 50 230 300 370 10 265 350 435

As with the analysis described earlier for frequencies in a range of 1kHz to 10 kHz (FIGS. 10A-11C), the data may be broken down to definedifferent regions 300 i at which effective sub-perception therapy isrealized below 1 kHz. For example, regions of effective sub-perceptiontherapy may be linearly bounded between various frequencies and the highand low pulse widths that define effectiveness. For example, at 10 Hz,PW(low)=265 microseconds and PW(high)=435 microseconds. At 50 Hz,PW(low)=230 microseconds and PW(high)=370 microseconds. Therefore, aregion 300 a that provides good sub-perception therapy is defined by thelinearly bounded region of points (10 Hz, 265 μs), (10 Hz, 435 μs), (50Hz, 370 μs), and (50 Hz, 230 μs). Table 2 defines the points thatlinearly bind each of the regions 300 a-300 g shown in FIG. 12A:

TABLE 2 region Bounded by points (Hz, μs) 300a (10, 265), (10, 435),(50, 370), (50, 230) 300b (50, 230), (50, 370), (100, 325), (100, 195)300c (100, 195), (100, 325), (200, 260), (200, 160) 300d (200, 160),(200, 260), (400, 225), (400, 140) 300e (400, 140), (400, 225), (600,200), (600, 120) 300f (600, 120), (600, 200), (800, 175), (800, 105)300g (800, 105), (800, 175), (1000, 150), (1000, 90)

Regions of sub-perception therapeutic effectiveness at frequencies at orbelow 1 kHz may be defined in other statistically-significant ways, suchas those described earlier for frequencies in the range of 1 kHz to 10kHz (FIGS. 11A-11C). For example, regions 300 i may be defined byreference to the pulse width at the middle of the ranges at eachfrequency, PW(middle). PW(middle) may comprise for example an averageoptimal pulse width reported by patients at each frequency, rather thanas a strict middle of an effective range reported by those patients.PW(high) and PW(low) may then be determined as a statistical variancefrom the average PW(middle) at each frequency, and used to set the upperand lower bounds of effective sub-perception regions. For example,PW(high) may comprise average PW(middle) plus a standard deviation orstandard error, or a multiples of such statistical measures; PW(low) maylikewise comprise average PW(middle) minus a standard deviation orstandard error, or a multiple of such statistical measures. PW(high) andPW(low) may also be determined from average PW(middle) in other ways.For example, PW(high) may comprise average PW(middle) plus a setpercentage, while PW(low) may comprise PW(middle) minus a setpercentage. In summary, one or more statistically-significant regions300 can be defined for the optimal pulse width and frequency data atfrequencies at or below 1 kHz that reduce pain using sub-perceptionstimulation without the side effect of paresthesia.

Also shown in FIG. 12A are average patient pain scores (NRS scores)reported by patients when optimal pulse widths are used for differentfrequencies at 1 kHz or below. Prior to receiving SCS therapy, patientsinitially reported pain scores with an average of 7.92. After SCSimplantation, and using the sub-perception stimulation at optimal pulsewidths with the ranges shown at each frequency, the patients' averagepain scores dropped significantly. At 1 kHz, 200 Hz, and 10 Hz, patientsreported average pain scores of 2.38, 2.17, and 3.20 respectively. Thusclinical significance with respect to pain relief is shown when theoptimal pulse widths are used at or below 1 kHz with sub-perceptiontherapy.

The optimal pulse width versus frequency data of FIG. 12A forfrequencies at or below 1 kHz is analyzed in FIG. 12B from theperspective of the middle pulse width, PW(middle) at each frequency (F).As shown, the relationships 310 a-310 d follows statisticallysignificant trends, as evidenced by the various regression models shownin FIG. 12B and summarized in Table 3 below:

TABLE 3 Correlation Regression coefficient model Relationship(PW(middle) in μs) R² Linear PW(middle) = −0.2F + 294.4 0.835 (310a)Polynomial PW(middle) = 0.0002F² − 0.461F + 332.38 0.936 (310b) PowerPW(middle) = 679.1x^(−0.23) 0.935 (310c) Logarithmic PW(middle) =−50.83ln(F) + 482.8 0.982 (310d)

Other fitting methods could be used to establish other informationrelating frequency and pulse width at which stimulation pulses areformed to provide sub-perception pain relief without paresthesia.

Regression analysis can also be used to define statistically relevantregions such as 300 a-300 g where sub-perception therapy is effective ator below 1 kHz. For example, and although not shown in FIG. 12B,regression can be performed for PW(low) v. F to set a lower boundary ofrelevant regions 300 i, and regression can be performed for PW(high) v.F to set an upper boundary of relevant regions 300 i.

Note that the relationship between optimal pulse width and frequencydepicted in FIG. 12A is not simply an expected relationship betweenfrequency and duty cycle (DC), as FIG. 12C shows. As was the case whenthe 1 kHz to 10 kHz frequency range was tested (FIG. 11A), the dutycycle of the optimal pulse widths is not constant at 1 kHz and below.Again, there is significance to the optimal pulse widths beyond a merescaling of the frequency. Nonetheless, most of the pulse widths observedto be optimal at 1 kHz and below are greater than 100 microseconds. Suchpulse widths are not even possible at higher frequencies. For example,at 10 kHz, both pulse phases have to fit within a 100 us period, so PWlonger than 100 are not even possible.

FIG. 12D shows further benefits achieved in using sub-perception atfrequencies of 1 kHz and below, namely reduced power consumption. Twosets of data are graphed. The first data set comprises the averagecurrent drawn by the battery in the patients' IPG or ETS (AVG Ibat) ateach frequency using the optimal pulse width for that patient (FIG. 12A)and the current amplitude A necessary to achieve sub-perceptionstimulation for that patient (again, this amplitude can vary for each ofthe patients). At 1 kHz, this average battery current is about 1700microamps. However, as the frequency is reduced, this average batterycurrent drops, to about 200 microamps at 10 Hz. The second data setlooks at power consumption from a different vantage point, namely thenumber of days that an IPG or ETS with a fully-charged rechargeablebattery can operate before recharge is required (“discharge time”). Aswould be expected based on the average battery current data, thedischarge time is lower at higher frequencies when the average batterycurrent is higher (e.g., about 3.9 days at 1 kHz, depending on variouscharging parameters and settings), and is higher at lower frequencieswhen the average battery current is lower (e.g., about 34 days at 10 Hz,depending on various charging parameters and settings). This issignificant: not only can effective sub-perception therapy be providedat 1 kHz and below when optimal pulse widths are used; powerconsumptions is greatly lowered, which places less stress on the IPG orETS, and allows it to operate from longer periods of time. As notedabove, excessive power consumption is a significant problem whensub-perception therapy is traditionally used at higher frequencies. Notethat the data of FIG. 12D could also be analyzed in terms of meancharge-per-second (MSC), as described earlier for the 1 kHz to 10 kHzdata (FIG. 10B).

Once determined, the information 350 relating frequency and pulse widthfor optimal sub-perception therapy without paresthesia can be stored inan external device used to program the IPG 10 or ETS 40, such as theclinician programmer 50 or external controller 45 described earlier.This is shown in FIG. 13, in which the control circuitry 70 or 48 of theclinician programmer or external controller is associated with regioninformation 100 i or relationship information 98 i for frequencies inthe 1 kHz to 10 kHz range, and region information 300 i or relationshipinformation 310 i for frequencies at or below 1 kHz. Such informationcan be stored in memory within or associated with the control circuitry.Storing of this information with the external device is useful toassisting the clinician with sub-perception optimization, as describedfurther below. Alternatively, and although not shown, the informationrelating frequency and pulse width can be stored in the IPG 10 or ETS40, thus allowing the IPG or ETS to optimize itself without clinician orpatient input.

Information 350 can be incorporated into a fitting module. For example,fitting module 350 could operate as a software module within clinicianprogrammer software 66, and may perhaps be implemented as an optionselectable within the advanced 88 or mode 90 menu options selectable inthe clinician programmer GUI 64 (FIG. 6). Fitting module 350 could alsooperate in the control circuitry of the IPG 10 or ETS 40.

The fitting module 350 can be used to optimize pulse width whenfrequency is known, or vice versa. As shown at the top of FIG. 13, theclinician or patient can enter a frequency F into the clinicianprogrammer 50 or external controller 45. This frequency F is passed tothe fitting module 350 to determine a pulse width PW for the patient,which is statistically likely to provide suitable pain relief withoutparesthesia. Frequency F could for example be input to the relationships98 i or 310 i to determine the pulse width PW. Or, the frequency couldbe compared to the relevant region 100 i or 300 i within which thefrequency falls. Once the correct region 100 i or 300 i is determined, Fcan be compared to the data in regions to determine a pulse width PW,which may perhaps be a pulse width between the PW+X and PW−X boundariesat the given frequency, as described earlier. Other stimulationparameters, such as amplitude A, active electrodes E, their relativepercentage X %, and electrode polarity P can be determined in othermanners, such as those described below, to arrive at a completestimulation program (SP) for the patient. Based on the data from FIG.10B, an amplitude near 3.0 mA might be a logical starting point, as thisamplitude was show to be preferred by patients in the 1 kHz to 10 kHzrange. However, other initial starting amplitudes may be chosen as well,which amplitudes for sub-perception therapy may be dependent onfrequency. The bottom of FIG. 13 shows use of the fitting module 350 inreverse—that is to pick a frequency given a pulse width. Note that inthe algorithms that follow or even when used outside of any algorithm,in one example, the system can allow the user to associate the frequencyand pulse width such that when the frequency or pulse width is changed,the other of the pulse width or frequency is automatically changed tocorrespond to an optimal setting. In some embodiments, associating thefrequency and pulse width in this manner can comprise a selectablefeature (e.g., in GUI 64) useable when sub-perception programming isdesired, and associating the frequency and pulse width can be unselectedor unselectable for use with other stimulation modes.

FIG. 14 shows an algorithm 355 that can be used to providesub-perception therapy to an SCS patient at frequencies of 10 kHz orlower, and summarizes some of the steps already discussed above. Steps320-328 describe the supra-perception sweep spot search. A user (e.g.,clinician) selects electrodes to create a bipole for the patient (320),for example, by using the GUI of the clinician programmer. This bipoleis preferably a symmetric biphasic bipole and may comprise a virtualbipole, as described earlier.

This bipole is telemetered along with other simulation parameters to theIPG or ETS for execution (321). Such other stimulation parameters canalso be selected in the clinician programmer using the GUI. As adefault, the frequency F can equal 90 Hz and the pulse width (PW) canequal 200 microseconds, although this is not strictly necessary andthese values can be modified. At this point, if the bipole provided bythe IPG or ETS is not supra-perception, i.e., if paresthesia is not feltby the patient, the amplitude A or other stimulation parameters can beadjusted to make it so (322). The bipole's effectiveness is then gaugedby the patient (324) to see how well the bipole is covering thepatient's pain site. NRS or other score rating systems can be used tojudge effectiveness.

If the bipole is not effective, or if it is still desired to search, anew bipole can be tried (326). That is new electrodes can be selectedpreferably in manner which moves the bipole to a new location, along apath 296 as described earlier with reference to FIGS. 7A-7D. This newbipole can then again be telemetered to the IPG or ETS (321) andadjustments made if necessary to render the bipole supra-perceptive(322). If the bipole is effective, or if the searching is done and amost effective bipole has been located, that bipole may optionally bemodified (328) prior to sub-perception therapy. Such modification asdescribed above can involve selecting other electrodes proximate to theselected bipole's electrodes to modify the field shape in the tissue toperhaps better cover the patient's pain. As such, the modification ofstep 328 may change the bipole used during the search to a virtualbipole, or a tripole, etc.

Modification of other stimulation parameters can also occur at thispoint. For example, the frequency and pulse width can also be modified.In one example, a working pulse width can be chosen which provides good,comfortable paresthesia coverage (>80%). This can occur by using afrequency of 200 Hz for example, and starting with a pulse width of 120microseconds for example. The pulse width can be increased at thisfrequency until good paresthesia coverage is noted. An amplitude in therange of 4 to 9 mA may be used for example.

At this point, the electrodes chosen for stimulation (E), theirpolarities (P), and the fraction of current they will receive (X %) (andpossible a working pulse width) are known and will be used to providesub-perception therapy. To ensure that sub-perception therapy isprovided, the amplitude A of the stimulation is titrated downward to asub-perception, paresthesia free level (330), and telemetered to the IPGor ETS. As described above, the amplitude A may be set below anamplitude threshold (e.g., 80% of the threshold) at which the patientcan just start to feel paresthesia.

At this point, it can be useful to optimize the frequency and pulsewidth of the sub-perception therapy that is being provided to thepatient (332). While the frequency (F) and pulse width (PW) used duringsweet spot searching can be used for sub-perception therapy, benefit ishad by additionally adjusting these parameters to optimal values inaccordance with the regions 100 i or relationships 98 i established atfrequencies in the 1 kHz to 10 kHz range, or the regions 300 i orrelationships 310 i established at frequencies at or below 1 kHz. Suchoptimization may use the fitting module 350 of FIG. 13, and can occur indifferent ways, and a few means of optimization 332 a-332 c are shown inFIG. 14. Option 332 a for instance allows the software in either theclinician programmer or the IPG or ETS to automatically select both afrequency (≤10 kHz) and pulse width using the region or relationshipdata correlating frequency to pulse width. Option 332 a might use theworking pulse width determined earlier (328), and choose a frequencyusing the regions or relationships. Option 332 b by contrast allows theuser (clinician) to specify (using the GUI of the clinician program)either the frequency (≤10 kHz) or the pulse width. The software can thenselect an appropriate value for the other parameter (pulse width orfrequency (≤10 kHz), again using regions or the relationships. Again,this option might use the working pulse width determined earlier toselect an appropriate frequency. Option 332 c allows the user to enterboth the frequency (≤10 kHz) and the pulse width PW, but in a mannerthat is constrained by the regions or the relationships. Again, thisoption may allow the use to enter the working pulse width and afrequency that is appropriate for that working frequency, depending onthe regions or relationships. The GUI 64 of the clinician programmermight in this example not accept inputs for F and PW that do not fallwithin the regions or along the relationships because such values wouldnot provide optimal sub-perception therapy.

Frequency or pulse width optimization can occur other ways that moreeffectively search the desired portion of the parameter space. Forexample, a gradient descent, binary search, simplex method, geneticalgorithm, etc. can be used for the search. A machine learning algorithmthat has trained using data from patients could be considered.

Preferably, when optimizing the frequency (≤10 kHz) and pulse width atstep 332, these parameters are selected in a manner that reduces powerconsumption. In this regard, it is preferable that the lowest frequencybe chosen, as this will reduce mean charge per second (MCS), reduce theaverage current drawn from the battery in the IPG or ETS, and thusincrease the discharge time, as discussed earlier with respect to FIGS.10B and 12D. Lowering the pulse width if possible will also reducebattery draw and increase the discharge time.

At this point all relevant stimulation parameters (E, P, X, I, PW, and F(≤10 kHz)) are determined and can be sent from the clinician programmerto the IPG or ETS for execution (334) to provide sub-perceptionstimulation therapy for the patient. It is possible that adjustment ofthe optimal pulse width and frequency (≤10 kHz) (332) may cause thesestimulation parameters to provide paresthesia. Therefore, the amplitudeof the current A can once again be titrated downward to sub-perceptionlevels if necessary (336). If necessary, the prescribed sub-perceptiontherapy can be allowed a period of time to wash in (338), although asmentioned earlier this may not be necessary as the supra-perceptionsweet spot search (320-328) has selected electrodes for situation thatwell recruit the patient's pain site.

If sub-perception therapy is not effective, or could use adjustment, thealgorithm can return to step 332 to selection of a new frequency (≤10kHz) and/or pulse width in accordance with the regions or relationshipsdefined earlier.

It should be noted that not all parts of steps of the algorithm of FIG.14 need be performed in an actual implementation. For example, ifeffective electrodes are already known (i.e., E, P, X), then thealgorithm may begin with sub-perception optimization using theinformation relating frequency and pulse width.

FIG. 15 shows another manner in which fitting module 350 (FIG. 13) canbe used to determine optimal sub-perception stimulation for a patient atfrequencies of 10 kHz or less. In FIG. 15, the fitting module 350 isagain incorporated within or used by an algorithm 105, which again canbe executed on the external device's control circuitry as part of itssoftware, or in the IPG 10. In the algorithm 105, the fitting module 350is used to pick initial pulse widths given a particular frequency.Algorithm 105 is however more comprehensive as it will test and optimizeamplitudes and further optimize pulse widths at different frequencies.As explained further below, algorithm 105 further optionally assists inpicking optimized stimulation parameters that will result in the lowestpower requirements that are most considerate of the IPG's battery 14.Some steps illustrated in FIG. 15 for algorithm 105 are optional, andother steps could be added as well. It is assumed that a sweet spotsearch for a patient being tested by algorithm 105 has already occurred,and that electrodes (E, P, X) have already been chosen and preferablywill remain constant throughout operation of the algorithm. However,this is not strictly required, as these electrode parameters can also bemodified, as described above.

Algorithm 105 begins by picking an initial frequency (e.g., F1) withinthe range of interest (e.g., ≤10 kHz). Algorithm 105 then passes thisfrequency to the fitting module 350, which uses the relationships and/orregions determined earlier to pick an initial pulse width PW1. Forsimplicity, fitting module 350 is illustrated in FIG. 15 as a simplelook up table of pulse width versus frequency, which can compriseanother form of information relating frequency and pulse width at whichstimulation pulses are formed to provide pain relief withoutparesthesia. Selection of a pulse width using fitting module 350 couldbe more sophisticated, as described earlier.

After selection of a pulse width for the given frequency, stimulationamplitude A is optimized (120). Here, a number of amplitudes are chosenand applied to the patient. In this example, the chosen amplitudes arepreferably determined using an optimal amplitude A determined at eachfrequency (see, e.g., FIG. 10B). Thus, amplitudes at A=A2, below (A1),and above (A3) are tried by the patient for a period (e.g., two dayseach). A best of these are picked by the patient. At this point, furtheradjustments to amplitude can be tried to try and hone in on an optimalamplitude for the patient. For example, if A2 is preferred, amplitudesslightly above (A2+Δ) and below (A2−Δ) below this can be tried for aperiod. If a lower value of A1 was preferred, an even lower amplitude(A1−Δ) can be tried. If a higher value of A3 was preferred, an evenhigher amplitude (A3+Δ) can be tried. Ultimately, such iterative testingof amplitude arrives at an effective amplitude for the patient that doesnot induce paresthesia.

Next, the pulse width can be optimized for the patient (130). As withamplitude, this can occur by slightly lowering or increasing the pulsewidth chosen earlier (350). For example, at a frequency of F1 and aninitial pulse width of PW1, the pulse width may be lowered (PW1−Δ) andincreased (PW1+Δ) to see if such settings are preferred by the patient.Further iterative adjustment of amplitude and pulse width may occur atthis point, although this is not illustrated.

In short, at a given frequency, an initial pulse width (350) (andpreferably also an initial amplitude (120)) are chosen for a patient,because it would be expected that these values would likely provideeffective and paresthesia-free pain relief. Nonetheless, because eachpatient is different, the amplitude (120) and pulse width (130) are alsoadjusted from the initial values for each patient.

Thereafter, the optimal stimulation parameters determined for thepatient at the frequency being tested are stored in the software (135).Optionally, a mean charge per second (MCS) indicative of the neural dosethe patient receives, or other information indicative of power draw(e.g., average Ibat, discharge time) is also calculated and also stored.If still further frequencies in the range of interest have not beentested (e.g., F2), they are then tested as just described.

Once one or more frequencies have been tested, stimulation parameterscan be chosen for the patient (140), using the optimal stimulationparameters stored earlier for the patient at each frequency (135).Because the stimulation parameters at each frequency are suitable forthe patient, the stimulation parameters chosen can comprise that whichresults in the lowest power draw (e.g., the lowest) MSC. This isdesired, because these stimulation parameters will be easiest on theIPG's battery. It might be expected that the stimulation parametersdetermined by algorithm 105 to have the lowest MCS would comprise thosetaken at the lowest frequency. However, every patient is different, andtherefore this might not be the case. Once the stimulation parametershave been chosen, further amplitude optimization can be undertaken(150), with the goal of choosing a minimum amplitude that providessub-perception pain relief without paresthesia.

It should be noted the use of the disclosed technique should notnecessarily be limited to the specific frequencies tested. Other datasuggests applicability of the disclosed technique to provide pain reliefwithout paresthesia at frequencies as low as 2 Hz.

Various aspects of the disclosed techniques, including processesimplementable in the IPG or ETS, or in external devices such as theclinician programmer or external controller to render and operate theGUI 64, can be formulated and stored as instructions in acomputer-readable media associated with such devices, such as in amagnetic, optical, or solid state memory. The computer-readable mediawith such stored instructions may also comprise a device readable by theclinician programmer or external controller, such as in a memory stickor a removable disk, and may reside elsewhere. For example, thecomputer-readable media may be associated with a server or any othercomputer device, thus allowing instructions to be downloaded to theclinician programmer system or external controller or to the IPG or ETS,via the Internet for example.

Although particular embodiments of the present invention have been shownand described, it should be understood that the above discussion is notintended to limit the present invention to these embodiments. It will beobvious to those skilled in the art that various changes andmodifications may be made without departing from the spirit and scope ofthe present invention. Thus, the present invention is intended to coveralternatives, modifications, and equivalents that may fall within thespirit and scope of the present invention as defined by the claims.

What is claimed is:
 1. A method for programming a spinal cord stimulatorimplanted in a patient and having a plurality of electrodes comprisingan array, the method comprising: (a) using pre-determined informationrelating at least a first stimulation parameter and at least a secondstimulation parameter to determine at least one stimulation parameterset for stimulation therapy that washes in to provide paresthesia-freepain relief within a period of one hour or less, wherein the firststimulation parameter and the second stimulation parameter areindicative of a timing of the stimulation therapy; and (b) programmingthe spinal cord stimulator with the determined at least one stimulationparameter set to provide the stimulation therapy that washes in toprovide the patient with the paresthesia-free pain relief within theperiod of one hour or less.
 2. The method of claim 1, wherein the periodis ten minutes or less.
 3. The method of claim 1, wherein the at leastone determined stimulation parameter set comprises at least onefrequency of the stimulation therapy that washes in to provide thepatient with the paresthesia-free pain relief within the period of onehour or less, or at least one pulse width of the stimulation therapythat washes in to provide the patient with the paresthesia-free painrelief within the period of one hour or less.
 4. The method of claim 3,wherein at least the at least one frequency is less than or equal to 10kHz or the at least one pulse width is greater than or equal to 21.8microseconds.
 5. The method of claim 4, wherein at least the at leastone frequency is less than or equal to 7 kHz or the at least one pulsewidth is greater than or equal to 33.4 microseconds.
 6. The method ofclaim 5, wherein at least the at least one frequency is less than orequal to 4 kHz or the at least one pulse width is greater than or equalto 42.1 microseconds.
 7. The method of claim 6, wherein at least the atleast one frequency is less than or equal to 1 kHz or the at least onepulse width is greater than or equal to 69.6 microseconds.
 8. The methodof claim 7, wherein at least the at least one frequency is less than orequal to 800 Hz or the at least one pulse width is greater than or equalto 105 microseconds.
 9. The method of claim 8, wherein at least the atleast one frequency is less than or equal to 600 Hz or the at least onepulse width is greater than or equal to 120 microseconds.
 10. The methodof claim 9, wherein at least the at least one frequency is less than orequal to 400 Hz or the at least one pulse width is greater than or equalto 140 microseconds.
 11. The method of claim 10, wherein at least the atleast one frequency is less than or equal to 200 Hz or the at least onepulse width is greater than or equal to 160 microseconds.
 12. The methodof claim 11, wherein at least the at least one frequency is less than orequal to 100 Hz or the at least one pulse width is greater than or equalto 195 microseconds.
 13. The method of claim 12, wherein at least the atleast one frequency is less than or equal to 50 Hz or the at least onepulse width is greater than or equal to 230 microseconds.
 14. The methodof claim 13, wherein at least the at least one frequency is less than orequal to 10 Hz or the at least one pulse width is greater than or equalto 265 microseconds.
 15. The method of claim 1, further comprisingprogramming the spinal cord stimulator with a plurality of stimulationparameter sets to provide the stimulation therapy that washes in toprovide the patient with the paresthesia-free pain relief within theperiod of one hour or less, wherein the plurality of stimulationparameter sets each define a duty cycle, wherein the duty cycles are notconstant among the plurality of stimulation parameter sets.
 16. Themethod of claim 1, wherein the pre-determined information comprises amathematical relationship relating at least the first stimulationparameter and at least the second stimulation parameter.
 17. The methodof claim 1, wherein the pre-determined information comprises a tablerelating at least the first stimulation parameter and at least thesecond stimulation parameter.
 18. The method of claim 1, wherein thepre-determined information comprises at least one region relating atleast the first stimulation parameter and at least the secondstimulation parameter.
 19. The method of claim 1, wherein the determinedstimulation set provides a mean charge per second (MCS) in the range of0.3 to 0.9 mC/s.
 20. The method of claim 1, wherein the stimulationtherapy is provided at a location in the array that is previouslydetermined by application of test pulses, wherein test pulses aresupra-perception.